Time-resolved (TR) near-infrared spectroscopy (NIRS) offers non-invasive clinical applications in monitoring the blood oxygenation, where absolute values of oxygenated and deoxygenated hemoglobin, and absorption and scattering coefficient, can be obtained. Various detectors have been utilized to realize a TR-NIRS system, such as PMT, SiPM, and SPAD. This paper proposed a prototype NIRS device implemented using a 128 x 128 lock-in pixel CMOS image sensor (CIS) based on the lateral electric field-charge modulator (LEFM) to achieve high time resolution. Preliminary experiments based on the reflectance of an agar phantom with varying absorption coefficient have been conducted and the ability to detect the changes in the absorption coefficient has been demonstrated. The reflectance of the agar phantom is directly observed by the image sensor, which was operated at a time-window of 900 ps with a sensor detection area of 2.9mm2 . The results suggest that a NIRS device using CIS is feasible, which opens the potential of a miniature wearable time-resolved NIRS device.
KEYWORDS: Tissues, Near infrared spectroscopy, Brain, Sensors, Natural surfaces, Absorption, Animal model studies, Fetus, Monte Carlo methods, Oximetry
We quantitatively investigated the measurement sensitivity of spatially resolved spectroscopy (SRS) across six tissue models: cerebral tissue, a small animal brain, the forehead of a fetus, an adult brain, forearm muscle, and thigh muscle. The optical path length in the voxel of the model was analyzed using Monte Carlo simulations. It was found that the measurement sensitivity can be represented as the product of the change in the absorption coefficient and the difference in optical path length in two states with different source–detector distances. The results clarified the sensitivity ratio between the surface layer and the deep layer at each source–detector distance for each model and identified changes in the deep measurement area when one of the detectors was close to the light source. A comparison was made with the results from continuous-wave spectroscopy. The study also identified measurement challenges that arise when the surface layer is inhomogeneous. Findings on the measurement sensitivity of SRS at each voxel and in each layer can support the correct interpretation of measured values when near-infrared oximetry or functional near-infrared spectroscopy is used to investigate different tissue structures.
Although fetal scalp blood sampling is an examination to assess fetal acidosis during the intrapartum period, it has not been widely used by obstetricians because of its invasiveness. We have developed a small, portable oximetry with a sensor attached to the examiner’s finger. Our previous report using this oximetry concluded that fetal head tissue oxygen saturation (StO2) correlated with umbilical cord artery blood pH. We investigated whether the association between StO2 and blood pH in mice could be validated using this oximetry. Eleven the Institute for Cancer Research (ICR) mice were measured using a near-infrared spectroscopy probe at the craniofacial site in a closed polyethylene bag while changing the oxygen concentration. A total of nine blood samples were collected and analyzed for pH. The StO2 and tissue blood pH showed a strong positive correlation (r=0.90 and P=0.0009). The StO2 and total hemoglobin index also showed a positive correlation (r=0.84 and P=0.0049). Thus, the results of the present study support those of our previous report on clinical cases and allow examiners to easily check the status of fetal acidosis. Fetal management using this oximetry might gain popularity with obstetricians in the near future.
The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor’s finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO2) with the new tissue oximeter. Neonatal StO2 was measured at any position of the head regardless of amount of hair. Neonatal StO2 was found to be around 77%. Fetal StO2 was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO2 without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO2 in any condition of the fetus.
Functional imaging of muscle oxygenation using NIRS is a promising technique for evaluation of the heterogeneity of muscle function and diagnosis of peripheral vascular disease or muscle injury. We have developed a 200-channel imaging system that can measure the changes in oxygenation and blood volume of muscles and that covers wider area than previously reported systems. Our system consisted of 40 probes, a multiplexer for switching signals to and from the probes, and a personal computer for obtaining images. In each probe, one two-wavelength LED (770 and 830 nm) and five photodiodes were mounted on a flexible substrate. In order to eliminate the influence of a subcutaneous fat layer, a correction method, which we previously developed, was also used in imaging. Thus, quantitative changes in concentrations of oxy- and deoxy-hemoglobin were obtained. Temporal resolution was 1.5 s and spatial resolution was about 20 mm, depending on probe separations. Exercise tests (isometric contraction of 50% MVC) on the thigh with and without arterial occlusion were conducted, and changes in muscle oxygenation were imaged using the developed system. Results showed that the heterogeneity of deoxygenation and reoxygenation during exercise and recovery periods, respectively, were clearly observed. These results suggest that optical imaging of dynamic change in muscle oxygenation using NIRS would be useful not only for basic physiological studies but also for clinical applications with respect to muscle functions.
Near-infrared spectroscopy (NIRS) is a very useful technique for noninvasive measurement of tissue oxygenation. Among various methods of NIRS, continuous wave near-infrared spectroscopy (CW- NIRS) is especially suitable for real-time measurement and for practical use. CW-NIRS has recently been applied in vivo reflectance imaging of muscle oxygenation and brain activity. However, conventional mapping systems do not have a sufficient mapping area at present. Moreover, they do not enable quantitative measurement of tissue oxygenation because conventional NIRS is based on the inappropriate assumption that tissue is homogeneous. In this study, we developed a 200-channel mapping system that enables measurement of changes in oxygenation and blood volume and that covers a wider area (30 cm x 20 cm) than do conventional systems. The spatial resolution (source- detector separation) of this system is 15 mm. As for the effcts of tissue inhomogeneity on muscle oxygenation measurement, subcutaneous adipose tissue greatly reduces measurement sensitivity. Therefore, we also used a correction method for influence of the subcutaneous fat layer so that we could obtain quantitative changes in concentrations of oxy- and deoxy- hemoglobin. We conducted exercise tests and measured the changed in hemoglobin concentration in the thigh using the new system. The working muscles in the exercises could be imaged, and the heterogeneity of the muscles was shown. These results demonstrated the new 200-channel mapping system enables observation of the distribution of muscle metabolism and localization of muscle function.
Near-infrared spectroscopy (NIRS) is a useful technique for noninvasive measurement of oxygenation of the brain and muscle. However, no accurate, quantitative algorithms for continuous wave NIRS (CW-NIRS) have yet been presented due to the following two problems. The first is that inhomogeneous tissue structure greatly affects measurement sensitivity. We previously reported on the influence of a fat layer on muscle oxygenation measurement and proposed a method for correcting the sensitivity. The second problem is that almost all algorithms for CW-NIRS have been experimentally determined, although al algorithm can be theoretically determined on the basis of diffusion theory if the mean optical pathlength in muscle in an in vivo state is known. In this study, we derived basic equations for a CW-NIRS algorithm based on diffusion theory, and we determined linear and nonlinear algorithms from mean optical pathlengths and validated them by results obtained from phantom experiments. For the determination of pathlength, the absorption and scattering coefficients of the muscle must be obtained by taking into account the influence of the fat layer. Laser pulses at 752 and 871 nm were applied to the forearms of the subjects, and the temporal point spread function (TPSF) was obtained by using a streak camera. The absorption and scattering coefficients of the muscle were determined by fitting the measured TPSF with that obtained by a Monte Carlo model consistingof skin, fat and muscle layers. From these coefficients, the mean optical pathlengths were obtained and the algorithms were determined.
KEYWORDS: Near infrared spectroscopy, Oxygen, Positron emission tomography, Tissues, Blood, Tissue optics, Oximeters, Signal detection, In vivo imaging, Light sources
The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by near-IR spectroscopy (NIRS). We have proposed a method for correcting the influence of a subcutaneous fat layer on muscle oxygenation measurements. In this study, we validated our correction method by measuring oxygen consumption rates of the forearm muscle and comparing the measurements with those obtained by other techniques. 31P-magnetic resonance spectroscopy and positron emission tomography (PET). In NIRS, Vo2mus was obtained from the falling rate of oxygenation in ischaemia tests. The values of Vo2mos were corrected using a curve of measurement sensitivity against fat layer thicknesses, which were measured by ultrasonography. The corrected Vo2mus showed greater values and less variation between individuals than did the uncorrected one. In the 31P-NMR measurements on 10 subjects, Vo2mus was estimated from changes in phosphocreatine. The corrected Vo2mus in NIRS correlated well with the measurements by 31P-NMR compared to the uncorrected Vo2mus. This result suggested that our correction method is valid. Vo2mus was also measured using PET in one of the authors. The measured values by NIRS. 31P-NMR and PET were 0.22, 0.17, 0.24 ml 100g-1 min-1, respectively. The measurement by NIRS using our correction method was in an acceptable range.
The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by reflectance NIRS. We have examined the influence of a subcutaneous fat layer on muscle oxygenation measurements. In this study, the influences of a fat layer and skin on muscle oxygenation measurement were investigated using Monte Carlo simulation and in vivo tests. Based on the experimental results, a correction curve for measurement sensitivity was determined. In the simulation, a 3-D model consisting of the epidermis, dermis, fat and muscle layers was used. In in vivo tests, measurement sensitivity was examined by measuring the falling rate of oxygenation in ischemia tests on the forearm using a newly developed multisensor type of oximeter with source-detector distances of 3-40 mm. Fat layer thickness was also measured by ultrasonography. The correction curve of measurement sensitivity against fat layer thickness was obtained from the results of simulation and in vivo tests. The measurements of oxygen consumption, calculated from the falling rates of oxygenation without correction, varied widely due to different thicknesses of fat layers. In contrast, the measurements of oxygen consumption with correction were almost the same (0.21 ±0.03 ml 100g-1 min-1). In this correction, the effect of skin on change in optical density was also taken into account using a detector with a short separation.
The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by reflectance NIRS. We have proposed a method for correcting the influence of a subcutaneous fat layer on muscle oxygenation measurement. In this study, this method was validated by measuring the peak-to-peak variation of muscle oxygenation in periodic exercise tests on the vastus lateralis and the falling rate of oxygenation in ischemia tests on the forearm. A newly developed multisensor probe with source- detector distances of 7-40 mm was used. THe probe, consisting of a two-wavelength LED and four photodiodes, was connected to a 4-channel tissue oxygen monitor. The fat layer thickness was also measured by ultrasonography. Results of the tests clearly showed that the presence of a fat layer greatly decreases the sensitivity of measurement and increases the light intensity at a detector. The correction factors of sensitivity were determined from this relationship and Monte Carlo simulation. The corrected oxygenation levels were quantitatively compared among subjects in spite of different fat layer thicknesses.
Two-layered phantom experiments were performed to examine the influence of a fat layer on measurement of muscle oxygenation using near-IR spectroscopy (NIRS). The phantom consisted of a fat-like layer and a muscle-like layer which were a mixture of agar and TiO2 powder and a suspension of washed bovine blood into 0.55 percent intralipid solution. An LED including 760 and 840 nm elements was used as the optical source, and the reflectance light was detected by photodiodes at source-detector distances of 20, 30 and 40 mm. Curves of optical density changes versus blood volume ratio were obtained with fat-like layer thickness of 0, 5, 10 and 15 mm. It was found that the change in optical density is significantly decreased and that the linearity of measurement characteristics clearly deteriorated by the presence of a fat layer. This strongly suggests that a new algorithm is needed for muscle oxygenation measurement to eliminate the influence of a fat layer. In addition to the phantom experiments, Monte Carlo simulations corresponding to the experiments were performed. Although the simulations showed similar results concerning the influence of a fat layer, it was noted that the changes in optical density obtained from simulations were lower than those of the phantom experiments. This discrepancy was though to be due to the light scattering caused by blood cells.
Although the inhomogeneity of tissue structure affects the sensitivity of tissue oxygenation measurement by reflectance near-infrared spectroscopy, few analyses of this effect have been reported. In this study, the influence of a subcutaneous fat layer on muscle oxygenation measurement was investigated by Monte Carlo simulation and experimental studies. In the experiments, measurement sensitivity was examined by measuring the falling rate of oxygenation in occlusion tests on the forearm using a tissue oxygen monitor. The fat layer thickness was measured by ultrasonography. Results of the simulation and occlusion tests clearly showed that the presence of a fat layer greatly decreases the measurement sensitivity and increases the light intensity at the detector. The correction factors of sensitivity were obtained from this relationship and were successfully validated by experiments on 12 subjects whose fat layer thickness ranged from 3.5 to 8 mm.
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