Comparison of Time resolved and Continuous wave Near infrared Spectroscopy Signals
Near-Infrared Spectroscopy Devices
A NIRS device exists out of a light source (emitting optode) to deliver light to the tissues at a known intensity and at two (or more) wavelengths surrounding the isobestic point, and a light detector (receiving optode), which measures the intensity of the exiting light. A computer translates the change in light intensity to clinical useful information ( Figs. 7.3 and 7.4 ).
Block diagram NIRS device (NIRO-300). A/D , analog to digital conversion; Amp , amplifier; CPU , central processing unit; D/A , digital to analog conversion; DU , display unit.
Commercial NIRS oximeters.
The position of the receiving optode from the light source can be either contralateral (transmission NIRS), which is most frequently used in infants, or ipsilateral (reflectance-mode NIRS). In addition, if two receiving optodes are used such as in SRS and NIRS, it is referred to as multidistance. Multidistance NIRS approach allows one to differentiate between light attenuation caused by skull and overlying tissues and light attenuation caused by cerebral tissue.
For cerebral oximetry, self-adhesive emitter/sensor pads applied to the skin of the forehead measure light attenuation noninvasively at a set distance from a NIRS-emitting light source. The absorption of the emitted light is directly proportional to chromophore concentration, the absorption coefficient of the chromophore, and the distance that the light travels between the emitting source and the detector, as stated in the Beer–Lambert law.
Oxyhemoglobin and deoxyhemoglobin have different and characteristic peak absorptions in the near-infrared spectrum, but both absorb light at an isobestic wavelength around 800 nm. The absorption of light at the isobestic wavelength allows for the measurement of total hemoglobin concentration. Thus, using a modification of the Beer–Lambert law, NIRS provides a measurement of the concentration of oxygenated hemoglobin in relation to total hemoglobin concentration.
Today, several NIRS devices are available ( Tables 7.2 and 7.3 ), and all have similar technology but with differences in the number and absolute value of wavelengths, in the computational algorithms, in the source of light, and in the distances between light emitted. The INVOS™, FORE-SIGHT™, EQUANOX™, and CerOx™ devices and the O3™ Regional Oximeter System are approved by Food and Drug Administration and Health Canada.
Table 7.2
Cited NIRS devices
- 1.
INVOS™ (Somanetics/Covidien/Medtronic, Inc., Boulder, CO)
- •
INVOS 3100
- •
INVOS 4100
- •
INVOS 5100
- •
- 2.
FORE-SIGHT™ (CAS Medical Systems, Branford, CN).
- •
FORE-SIGHT MC-2000
- •
FORE-SIGHT 2040
- •
FORE-SIGHT ELITE
- •
- 3.
EQUANOX™ (Nonin Medical Inc., Plymouth, MN).
- •
EQUANOX Classic 7600
- •
EQUANOX Advanc 8004 CA
- •
- 4.
CerOx™ (Ornim Medical, Lod, Israel).
- •
CerOx™
- •
- 5.
NIRO™ (Hamamatsu Photonics, Hamamatsu City, Japan)
- •
NIRO-500
- •
NIRO-300
- •
NIRO-200 XN
- •
- 6.
TOS-96™ (Tostec, Tokyo, Japan)
- •
TOS-96™
- •
- 7.
O3™ Regional Oximetry (Masimo, Irvine, CA)
CA , California; CN , Connecticut; CO , Colorado; MN , Minnesota; USA , United States.
Table 7.3
Some near-infrared spectroscopy devices cited in clinical setting
| Company | Device | Variables | Wavelengths (nm) | Type |
|---|---|---|---|---|
| CAS Medical | FORE-SIGHT™ ELITE, (CAS Medical Systems, Branford, CN) | Cerebral and somatic tissue oxygen saturations | 690, 778, 800, 850 nm | Saturation (absolute) |
| COVIDIEN | INVOS™ 5100, (Somanetics/Covidien, Inc., Boulder, CO) | Cerebral and somatic tissue oxygen saturation | 730, 810 nm | Saturation |
| Hamamatsu Photonics | NIRO™ 300, (Hamamatsu Photonics, Hamamatsu City, Japan) | Cerebral (HbO 2, HHb, CytOx, TOI) | 775, 825, 850, 905 nm | Concentration and saturation |
| Masimo | O3™ (Masimo, Irvine, CA) | Cerebral oxygen saturation | 730, 760, 805, 880 nm | Saturation (absolute) |
| Nonin Medical | EQUANOX Advance™ 8004CA, (Nonin Medical Inc., Plymouth, MN) | Cerebral and somatic tissue oxygen saturations | 730, 760, 810, 880 nm | Saturation |
| Ornim Medical | CerOx™, (Ornim Medical, Lod, Israel) | Cerebral and somatic blood flow and saturation | Ultrasound-tagged near-infrared spectroscopy (UT-NIRS), and three wavelengths between 780 and 830 nm | Saturation and blood flow |
| TOSTEC Co. | TOS-96™, (TOSTEC Co., Tokyo, Japan) | Cerebral rSO 2 | 750, 850, 810 nm | Saturation |
INVOS™
The INVOS™ system utilizes near-infrared light at wavelengths that are absorbed by hemoglobin (730 and 810 nm). It has two receivers at different distances from the light emitter to correct for surface tissue overlying the brain ( Fig. 7.5A ).
NIRS sensors: (A) one emitter and two detectors like CASMED FORE-SIGHT, Covidien INVOS, and O3 Regional sensors, and (B) two emitters and two detectors like Nonin's EQUANOX Advance sensor.
Sensors for light detection are placed 30 and 40 mm from the light-emitting diode. For INVOS™ the assumed arterial:venous ratio is 25%/75%, upon which the oximetry values are calculated. Light travels from the sensor's light-emitting diode to either a proximal or distal detector, permitting separate data processing of shallow and deep optical signals. INVOS™ system's ability to localize the area of measurement, called spatial resolution, has been empirically validated in human subjects. Data from the scalp and surface tissue are subtracted and suppressed, reflecting rSO 2 in deeper tissues. A single absolute value, rSO 2 , is calculated by an algorithm, which is thought to be independent of path length. The same concept applies to somatic monitoring.
FORE-SIGHT™
On the FORE-SIGHT™ monitor, the sensors are 15 and 50 mm from the laser-generated light source. It uses laser-emitting diodes to generate light at four different wavelengths (690, 778, 800, and 850 nm), and " wavelength"-resolved spectroscopy, with two detectors. The scalp detector samples returning light from the extracranial tissue, whereas the brain detector samples returning light signal from both the brain and the extracranial tissue ( Fig. 7.5A ). The signal from the scalp detector is used to cancel extracerebral interference from the signal of the brain detector to obtain information that mostly comes from the brain.
The SctO 2 is determined from the ratio ((HbO 2 )/(HbO 2 + HHb)) × 100%, which assumes a mixture of venous to arterial to venous blood of 70/30, respectively. It is claimed the monitor measures absolute values that indicate a patient's cerebral tissue oxygen saturation status.
EQUANOX™
EQUANOX™ utilizes four wavelengths (730, 760, 810, and 880 nm) of light to measure the balance of oxy- and deoxyhemoglobin, while compensating for tissue factors that reduce rSO 2 accuracy. It utilizes a dual light-emitting and -detecting sensor architecture, which has been shown to more effectively target the cerebral cortex, eliminating surface artifacts that interfere with measurement accuracy.
The EQUANOX™ Classic 7600 monitor system uses two separate sets of light-emitting diodes and two light sensors that are 20 and 40 mm from the light source ( Fig. 7.5B ). It uses a more complex analysis process whereby the 40-mm detector for one light source serves as the proximal sensor for the other device.
The EQUANOX™ Advance series cerebral/somatic oximetry system effectively isolates targeted tissue and automatically considers the light attenuation changes caused by myelination variation. Also, age, skin color, and hematocrit did not affect these values.
CerOx™
The CerOx™ monitor (Ornim Medical) uses a laser light source and has one sensor. This method allows the light-penetration profile to be assessed, thereby enabling the light to be focused on the desired depth and volume of brain tissue. The monitor employs a new technology, ultrasound-tagged near-infrared spectroscopy (UT-NIRS), leveraging the effect of ultrasound waves on light to tag it. This technology uses the ability of near-infrared light to measure regional oxygen saturation in combination with ultrasound that can achieve localization via the acousto-optic effect. Monitoring of the reflected ultrasound provides an additional indicator of local tissue cerebral blood flow. It uses NIRS and ultrasound to assess cerebral oxygenation and blood flow in a noninvasive manner.
The probe emits light at three wavelengths between 780 and 830 nm and detects the scattered light at a distance of 12 mm from the emitter. Low-power ultrasound waves are also emitted to induce the UT-NIRS signal by modulating light via the acousto-optic effect. A spectral analysis is then performed to calculate the saturation of hemoglobin within the region of interest.
NIRO™
The original NIRO-500™ measured only changes in concentrations from an arbitrary point using the modified Beer–Lambert law (MBL). Another clinical tissue oxygenation monitor has been developed, the NIRO-300™, which measures the concentration changes (ΔHbO 2 , ΔHHb, ΔCytOx) by MBL and a TOI by SRS ( Fig. 7.3 ). The following variables are monitored by NIRO-300™:
- 1.
oxygenated hemoglobin (ΔHbO 2 ),
- 2.
deoxygenated hemoglobin (ΔHHb),
- 3.
total hemoglobin (ΔTHb) = ΔHbO 2 + ΔHHb,
- 4.
oxidized cytochrome aa 3 (ΔCytOx).
- 5.
tissue oxygen index (TOI) = (HbO 2 /THb) × 100
Measurements of ΔHbO 2 , ΔHHb, and ΔCytOx start at zero level because the absolute values of these parameters are not known. However, TOI is reported as an absolute value. This is attributed to the use of SRS, which incorporates several detectors housed in a single probe placed 4–5 cm from the source ( Fig. 7.5B ). It uses four wavelengths: 775, 825, 850, and 905 nm. Combination of these multidistance measurements of optical attenuation with the usual multiwavelength spectroscopy data allows calculation of the relative concentrations of HHb and HbO 2 in the illuminated tissue and therefore an estimate of the mean tissue hemoglobin saturation even though the component HbO 2 can be reported only as changes.
NIRO-200NX™ is a new tissue (cerebral and somatic) oxygen monitor machine introduced by Hamamatsu. It measures TOI and normalized tissue hemoglobin index (nTHI), showing the percentage change in the amount of initial hemoglobin, as well as ΔHbO 2 , ΔHHb, and ΔTHb, all in real time. The probe emits light at three wavelengths: 735, 810, and 850 nm.
TOS-96™
TOS-96™ (TOSTEC Co., Tokyo, Japan) is attached to the patient's forehead for monitoring the rSO 2 in the bilateral frontal lobes at a depth of approximately 3 cm beneath the skin. Each sensor consists of one silicon diode that receives the signal and three laser-emitting diodes (LEDs) that emit near-infrared light of wavelengths 750, 850, and 810 nm, for measurement of HHB, HbO 2 , and Hb level, respectively. The rSO 2 % is calculated from the NIRS data, using the following equation :
<SPAN role=presentation tabIndex=0 id=MathJax-Element-3-Frame class=MathJax style="POSITION: relative" data-mathml='rSO2=(oxyHb)/(oxyHb+deoxyHb)×100′> rSO 2 = ( oxyHb ) / ( oxyHb + deoxyHb ) × 100 rSO2=(oxyHb)/(oxyHb+deoxyHb)×100
rSO 2 = ( oxyHb ) / ( oxyHb + deoxyHb ) × 100
Regional O3™ System
The O3™ Regional Oximeter System (O3™ System) (Masimo Corporation, Irvine CA), which consists of the O3 Module and O3™ Sensor, is a patient-connected, LED-based technology, noninvasive oximeter designed to continuously measure and monitor rSO 2 . O3™ Regional Oximetry is intended for use as an adjunct monitor of absolute and trended rSO 2 of blood in the cerebral region under the sensors. The O3™ System's operating principle is based on multidistance diffuse reflectance NIRS and consists of one light emitter and two photodetectors. It uses four wavelengths of light to examine a cross-section tissue microvasculature (a mixed bed of arterioles, capillaries, and venules) and analyzes the received light for calculating deep-tissue oxygen saturation. For the purpose of comparison against a standard reference, blood in the cerebral tissue is approximated as a mixture of venous (70%) and arterial (30%) blood. The main advantage of this technology is that the information is displayed simultaneously on the monitor with concurrent bilateral SedLine, pulse oximetry, capnography, and oxygen reserve index (ORI). SedLine Sedation Monitor is a patient- connected, 4-channel processed electroencephalogram (EEG) monitor designed specifically for intraoperative or intensive care unit (ICU) use. It displays electrode status, EEG waveforms, density spectral array (DSA), and patient state index (PSI). The ORI is a novel pulse oximeter–based nondimensional index that ranges from 1 to 0 as PaO 2 decreases from about 200 to 80 mm Hg and is measured by optically detecting changes in SvO 2 after SaO 2 saturates to the maximum. The O3™ System was validated by Redford et al. in 27 healthy volunteers undergoing controlled hypoxia.
Comparison Between Different Near-Infrared Spectroscopy Machines
Several studies compared readings obtained from different NIRS devices in various clinical situations, but the results are not encouraging. Hessel et al. found an oxygen level–dependent difference between INVOS™ 5100C and FORE-SIGHT™ cerebral oximeters in 12 term newborn infants. Their readings differed as much as 20% at the lowest range of saturations. Others compared INVOS™ 5100C and EQUANOX™ 7600 cerebral oximeters during cardiac surgery and found that both devices are not interchangeable with a mean bias of −5.1% and limits of agreement of ±16.37% when comparing absolute values. Dix et al. compared five sensors of three commonly used devices INVOS™ (INVOS neonatal, INVOS pediatric and INVOS adult sensors), FORE-SIGHT (neonatal sensor), and EQUANOX (adult sensor) in preterm neonates. They found good correlation between different NIRS sensors. However, substantial differences between absolute cerebral oxygenation values measured with the adult sensor and the pediatric and neonatal sensors range between 10% and 14%, being higher in the pediatric and neonatal sensors.
Interestingly, Bickler et al. studied factors that affect the performance of five cerebral oximeters (EQUANOX 7600 in 3- and 4-wavelength versions, FORE-SIGHT, INVOS TM 5100C, and the NIRO-200NX) during stable isocapnic hypoxia in volunteers. Six steady states of arterial oxygen saturation (SaO 2 ) levels between 100% and 70% were achieved by changing inspired oxygen (FIO 2 ), while end-tidal carbon dioxide (ETCO 2 ) was maintained constant. At each plateau, simultaneous blood samples from the jugular bulb and radial artery were analyzed with a hemoximeter. Each cerebral oximeter's bias was calculated as the difference between the instrument's reading (cerebral saturation) with the weighted saturation of venous and arterial blood, as specified by each manufacturer (INVOS: 25% arterial/75% venous; FORE-SIGHT, EQUANOX, and NIRO: 30% arterial/70% venous). A calculated bias was observed between the oximeters readings and the weighted values of arterial and cerebral mixed venous oxygen saturation. FORE-SIGHT™, NIRO-200NX™, and EQUANOX (3 wavelength version) have significant positive mean bias during hypoxia. In addition, there was significant variation between-subject and between-instrument with substantial variably in baseline readings between the five instruments.
Such results indicate that absolute cerebral oxygenation values cannot be provided by the five devices, and the absolute threshold of saturation that results in tissue damage is difficult to be determined. It is clear that measurements were not quite equivalent and varied depending on the chosen NIRS device, and different NIRS devices provide us with different values. In addition, there were significant differences in absolute values and dynamic measurements between different devices, and there was a large intra- and interindividual variability and a variable repeatability.
In a multicenter trial conducted by Deschamps et al., three devices were used. Although the goal of the study was not to compare them, the number of decrease in rSO 2 below 20% with the different NIRS devices was 1.5, 1.7, and 2.3 desaturations/patient recruited with the FORE-SIGHT, EQUANOX Classic 7600, and INVOS 5100C-PB, respectively. A systematic review of cerebral oxygenation devices was published in 2014 by Douds et al. Most of the studies, so far, have been done with the INVOS.
Such differences could be explained by the following: First the differences in technical aspects such as different algorithms, near-infrared light emission source, number of wavelengths, or scattering subtraction may be underlying causes. Two, since no real reference value exists for rSO 2 , it is not possible to state if one monitor is more valid than another. Finally, the accuracy of quantitative data by NIRS is limited by inaccuracies in the estimation of optical path length for light transmitted through tissue. Until real-time path length measurements are incorporated, relative changes will form the basis of NIRS.
Comparison of Cerebral Near-Infrared Spectroscopy and Jugular Bulb Oxygen Saturation
Since cerebral NIRS and jugular bulb oxygen saturation (SjO 2 ) both aim to reflect cerebral oxygenation, it is important to see how well the two correlate ( Table 7.4 ). Although SjO 2 and rSO 2 are known to be similar in some studies, the limits of agreement are wide in others. Also, there was no clear consistent agreement between SjO 2 saturation and rSO 2 measured by different NIRS machines. However, narrow limits of agreement appeared when considering rSO 2 as 70%–75% venous, and 25%–30% arterial. This could be explained by the global nature of SjO 2 , versus the small region of brain tissue reflected in rSO 2 , by extracranial contamination of the NIRS signal and lack of gold standard for NIRS measurements. Such results showed that the two methods are not interchangeable. Which one is "right" remains a subject of controversy, since both methods probably measure different entities and/or each monitor offers a different window for brain monitoring.
Table 7.4
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