Monitoring blood loss with near infrared spectroscopy

Experimental research has shown correlation between near infrared spectroscopy (NIRS) and blood loss, but these findings have not been validated in man. Ten blood donors were monitored before, during and for 10 min after blood collection (470 ml) with NIRS. A Somanetics INVOS 4100 oximeter monitored regional haemoglobin saturation in the cerebral cortex (cSO(2)-left frontal area) and from the left calf (pSO(2)). A Critikon 2001 Cerebral Redox Model monitored total (tHb), oxygenated (O(2)Hb) and deoxygenated (HHb) haemoglobin from the right calf. The oxygenation index [HbD]=[O(2)Hb]-[HHb] was derived from the data. cSO(2) (P<0.001), pSO(2) (P<0.001) and HbD (P=0.001) decreased during blood collection. Maximum changes occurred 10 minutes after collection for cSO(2), with a mean fall (95% C.I.) of 2.5 (-0.06-4.86)%, at the end of blood collection for pSO(2), with a mean fall (95% C.I.) of 3 (0.74-5.26)% and after 8% of blood volume loss for HbD, with a mean fall (95% C.I.) of 7.2 (2.25-12.16). Cerebral and peripheral oxygenation did not recover after blood collection. There was good correlation between NIRS parameters and blood loss. NIRS is a potentially useful technique for monitoring blood loss in humans. Further research is needed to define its role in clinical practice.     

Quantitation of cerebral blood volume in human infants by near-infrared spectroscopy

Current methods for measuring cerebral blood volume (CBV) in newborn infants are unsatisfactory. A new method is described in which the effect of a small change (5-10%) in arterial oxygen saturation (SaO2) on cerebral oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] concentration is observed by near-infrared (NIR) spectroscopy. Previous experiments in which the NIR absorption characteristics of HbO2 and Hb and the pathlength of NIR light through the brain were defined allowed changes in [HbO2] and [Hb] to be quantified from the Beer-Lambert law. It is shown here that CBV can then be derived from the expression CBV = (delta[HbO2] - delta[Hb])/(2. delta SaO2.H.R.), where H is the large vessel total hemoglobin concentration and R to the cerebral-to-large vessel hematocrit ratio. Observations on 12 newborn infants with normal brains, born at 25-40 wk of gestation and aged 10-240 h, gave a mean value for CBV of 2.22 +/- 0.40 (SD) ml/100 g, whereas mean CBV was significantly higher 3.00 +/- 1.04 ml/100 g in 10 infants with brain injury born at 24 to 42 wk of gestation and aged 4-168 h (P less than 0.05).     

Changes of cerebral blood oxygenation and optical pathlength during activation and deactivation in the prefrontal cortex measured by time-resolved near infrared spectroscopy

To determine the alterations in optical characteristics and cerebral blood oxygenation (CBO) during activation and deactivation, we evaluated the changes in mean optical pathlength (MOP) and CBO induced by a verbal fluency task (VFT) and driving simulation in the right and left prefrontal cortex (PFC), employing a newly developed time-resolved near infrared spectroscopy, which allows quantitative measurements of the evoked-CBO changes by determining the MOP with a sampling time of 1 s. The results demonstrated differences in MOP in the foreheads with the subjects and wavelength; however, there was no significant difference between the right and left foreheads (p > 0.05). Also, both the VFT and driving simulation task did not affect the MOP significantly as compared to that before the tasks (p > 0.05). In the bilateral PFCs, the VFT caused increases of oxyhemoglobin and total hemoglobin associated with a decrease of deoxyhemoglobin, while the driving simulation task caused decreases of oxyhemoglobin and total hemoglobin associated with an increase of deoxyhemoglobin; there were no significant differences in evoked-CBO changes between the right and left PFC. The present results will be useful for quantitative measurement of hemodynamic changes during activation and deactivation in the adults by near infrared spectroscopy.     

Changes in cerebral near infrared spectroscopy parameters during manual acupuncture needle stimulation]

Near-infrared spectroscopy (NIRO 300, Hamamatsu Photonics, Japan) was used to monitor human cerebral function in the central region during manual acupuncture needle stimulation of the large intestine 4 (LI.4) point in 16 adult volunteers (9 females, 7 males; mean age 23.9 +/- 6.0 (SD) years, range 19-45 years). We found a significant (p < 0.001) decrease in oxyhaemoglobin after needle insertion and stimulation (duration 20 sec.), accompanied by an increase (p = 0.003) in deoxyhaemoglobin. A repeat stimulation showed similar effects. Cytochrome oxidase aa3 remained unchanged during stimulation. The results demonstrate that near-infrared spectroscopy may be a noninvasive method of measuring regional changes in cerebral haemodynamics resulting from peripheral acupuncture stimulation.     

Skeletal muscle oxygenation monitoring by near infrared spectroscopy.

The oxygenation of human forearm muscle tissue was studied using an optic fiber fast scanning spectrophotometer. We investigated near infrared (700-1100 nm) hemoglobin (Hb) and myoglobin (Mb) spectral changes in flow and/or oxygen-limited conditions. The superimposition of deoxy Hb and deoxy Mb spectra was confirmed "in vivo" on perfluorocarbon-blood exchanged transfused rats. Oxygenation changes were evaluated in 15 volunteers during 10 min forearm arterial occlusion. Rapid desaturation occurred until a plateau was reached after about 4 min, suggesting rapid anaerobic glycolytic activation.     

Water near lipid membranes as seen by infrared spectroscopy

The ordering and H-bonding characteristics of the hydration water of the lipid 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) were studied using polarized infrared spectroscopy by varying either the temperature or the relative humidity of the ambient atmosphere of multibilayer samples. The OH-stretching band of lipid-bound water was interpreted by a simplified two-state model of well-structured, low density “network” water and of less-structured dense “multimer” water. The IR-spectroscopic data reflect a rather continuous change of the water properties with increasing distance from the membrane and with changing temperature. Network and multimer water distribute across the whole polar interphase with changing composition and orientation. Upon dehydration the fraction of network water increases from about 30 to 60%, a value which is similar to that in supercooled water at −25°C. The highly ordered gel phase gives rise to an increased fraction of structured network water compared with the liquid crystalline phase. The IR order parameter shows that the water dipoles rearrange from a more parallel towards a more perpendicular orientation with respect to the membrane normal with progressive hydration. Dedicated to Prof. K. Arnold on the occasion of his 65th birthday.     

Investigation of DNA structural changes by infrared spectroscopy

DNA-oriented samples of various origins were studied under different conditions of humidiity and sodium chloride content by means of infrared spectroscopy. (1) Oriented DNA (M. Lysodeikticus, E. coli, calf thymus and salmon sperm) films at 3–4% sodium chloride yield polarized spectra which show drastic changes at relative humidities (r.h.) between 94% and 0% indicative of conformational changes: B form → a form → disordered form The measurements of the infrared dichroism at frequencies of about 1230 cm^?1 and at about 1090 cm^?1 allow one to determine the orientation of the phosphate group, whereas the measurements at 1710 cm^?1 characterize the base orientation. At humidities higher than 90% r.h. (B form) the bisector of OPO forms an angle of 70° relative to the helix axis, whereas at lower humidities, between 75% and 50% r.h. (A form) a rotation to about 45° is observed. Simultaneously, the 0—0 line of phosphate group changes its orientation from 55° to 65° to the helix when B → A transition takes place. The results are in general agreement with that of X-ray diffraction and allow one to determine the orientation of the phosphate group with greater precision. (2) The B–A conformational change is not observed for satellite DNA, isolated from Cancer pagurus, of which the guanine + cytosine content is below 5%. As a function of decreasing humidities, one observes the transition: B form → disordered form A diagram of conformational changes of DNA's as a function of base composition and of r.h., suggests that B–A transition will occur for DNA of relatively higher G + C content, whereas for high (A + T) content, base sequence may be of importance. The B–A transition is prevented in DNA at a relatively high or very low sodium chloride content.     

Examining water in model membranes by near infrared spectroscopy and multivariate analysis

By exploiting the sensitivity of the NIR spectrum, particularly the first overtone of water, to the number and strength of hydrogen bonds, the hydrogen bond network and water polymerization in membranes of DMPA (1,2-dimyristoyl-sn-glycero-3-phosphate) and DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) was investigated as a function of the temperature and the presence of this two phospholipids having the same tail but different polar head. Principal components analysis performed on the spectra was used to disclose subtle spectral changes that mirror the alteration of the vibrational energy of the water O-H bonds, as a measure of the H-bond network. Temperature showed a dominating effect on the H-bond network. Increasing temperatures diminished the number of strongly H-bonded water molecules and increased the number of weakly H-bonded waters. This main effect of temperature was missing after the subtraction of the pure water spectra from the lipid-containing ones. An intriguing secondary effect of temperature was also revealed. Phospholipids exhibited an effect qualitatively similar to that of the temperature. DMPA, and particularly DMPC, disrupted the H-bond network in the neighboring lipid-water interface, reducing water polymerization and strengthening the water O-H bonds. The type of the polar head affects the H-bonds more than duplicate the concentration of the lipid. A connection between head group structure and the effect on the H-bonds network, and the existence of two populations of water molecules are discussed.     

A novel method for analyzing thick tablets by near infrared spectroscopy

A near-infrared (NIR) spectroscopic method to determine content uniformily of a large, thick tablet using an approach that could facilitate future validations has been developed. A CT ibuprofen 800-mg tablet weighs about 1150 mg and is about 18.6 mm wide and 7.6 mm thick. The FT NIR spectrometer was optimized for transmission spectra of the tablets by moving it to the sample compartment and placing it immediately behind the tablet. In spite of this dedicated setup, the transmission spectra obtained were very poor, indicating that the NIR radiation was not reaching the detector. The spectra of the tablet improved with use of a simple preparation in which a flat-face die applies pressure of 20 000 psi to the tablet, this reduced the thickness of the tablet from 7.6 mm to 3.6 mm. A calibration model was developed for tablets with drug content ranging from 70% to 130% of label. The calibration model was tested using a validation set of tablets with a drug content of 752, 800, and 848 mg. The results obtained were within 1.5% of the known drug content of the validation set, tablets. Even with the sample preparation, the content uniformity results of 10 tablets could be determined using this method in less than 1 hour. The approach described in this article could also be used to validate NIR content uniformity methods for orther formulations. Published: July 12, 2001.     

Measurement of cerebral oxygenation in neonates after vaginal delivery and cesarean section using full-spectrum near infrared spectroscopy

To investigate whether or not the mode of delivery produces differences in cerebral oxygenation, cerebral hemoglobin oxygen saturation was measured using full-spectrum near infrared spectroscopy in 26 healthy term newborn infants immediately after birth. Infants in group 1 (n=20) were delivered vaginally, and those in group 2 (n=6) by elective cesarean section. Arterial oxygen saturation in the right hand was also measured simultaneously using a pulse oximeter. Changes in arterial oxygen saturation showed no significant difference between the two groups. The mean+/-S.D. of cerebral hemoglobin oxygen saturation in group 1 increased rapidly after birth, from 29+/-17% at 2 min to 68+/-6% at 8.5 min, followed by an almost constant value (66+/-7% at 15 min). In comparison, cerebral hemoglobin oxygen saturation in group 2 also increased rapidly until 8.5 min, but after this time decreased significantly to 57+/-5% at 15 min after birth. This indicates that the mode of delivery has a marked influence on cerebral oxygenation immediately after birth.     

Influence of steroids on hydrogen bonds in membranes assessed by near infrared spectroscopy

The covalent OH bonds of water vibrate and absorb radiation in the near infrared (NIR) region at wavelengths that vary according to the strength of the bonds which, at the same time, are sensitive to the number and/or strength of hydrogen bonds. By means of multivariate analytical tools, such spectral shift was exploited to study the effect of temperature, 25-hydroxycholesterol and progesterone on the H-bonded network of water in DMPA membranes. Temperature was found as the dominating factor altering the NIR spectra of water and then the H-bonds. Increasing temperatures disrupt the H-bonds network, strengthening the OH covalent bonds. The disruption of the H-bonds along the 13–58 °C range was noticeably greater than that caused by lipids or steroids at 500 μM. The H-bonded network of the interfacial water in DMPA membranes was disrupted by the presence of 25-hydroxycholesterol, but no significant disruption was observed in the presence of progesterone. The reduction of the H-bonds entails a reduction in the aggregation of the interfacial water by a reduction in the number of H-bonded molecules. It is proposed that the number of water molecules bonded with two H-bonds diminishes and the number of molecules with no H-bond increases roughly at similar proportions, with a constant population of molecules with one H-bond. The opposed effects of steroids are discussed in the context of their opposed effects on the phase state of membranes, the membrane water content and the steroid molecular structure.     

Transcranial oximetry using fast near infrared spectroscopy can detect failure of collateral blood supply in humans

We tested the hypothesis that transcranial oximetry by fast scanning near infrared spectroscopy can detect local desaturation of hemoglobin in arterial vessels of cerebral circulation with impaired blood supply. A total of 74 near infrared spectroscopy recordings were taken from the intact skull of humans. Perfusion of the hemisphere under the detector was assessed in one of four groups: (1) healthy volunteer; (2) patient, unaffected side; (3) patient, affected side with intact collateral blood supply; (4) patient, affected side, impaired collateral blood supply. Transcranial saturation was 0.90+/-0.01 (all values reported as mean+/-S.E.) in healthy volunteers (n=24), 0.92+/-0.008 in the unaffected hemisphere of patients (n=23), 0.92+/-0.001 in the affected side if collateral supply with blood was intact (n=16). There was no statistical significance between these groups. Saturation in affected hemispheres with impaired collateral blood supply (n=9) was 0.81+/-0.028, which was significantly different from all other groups (P<0.05, one way-ANOVA). We conclude, that transcranial pulse oximetry can detect local hypoxia if collateral blood supply fails.     

Age-associated alteration of muscle oxygenation measured by near infrared spectroscopy during exercise

The influence of ageing on the capacity to increase muscle oxygen delivery during exercise is unclear. This was investigated by comparing the evolution of Near InfraRed Spectroscopy (NIRS) in 10 old (67 +/- 5 years, Old group) and 13 young subjects (27 +/- 4 years, Young group), during a progressive maximal exercise. The NIRS probe was placed on the vastus lateralis; muscle oxygen saturation - IR-SmO(2) - values were expressed on a scale using an arterial occlusion as the lower reference point and the subsequent reactive hyperaemia as the upper reference point. Resting IR-SmO( 2) was found to be significantly lower in the Old as co mpared to the Young group. During exercise, VO(2) increased similarly as a function of the workload whereas IR-SmO(2) decreased faster in old subjects than in young ones. Conversely, when expressed at the same percentage of VO( 2max), IR-SmO(2) followed a similar evolution in both groups from rest to maximal exercise (27.3 +/- 16.7 vs 24.3 +/- 12.9% decrease, in Old and Young group, respectively, NS). Thus, the initial difference remained constant between the two groups. During recovery, the time to recover the signal variation was not different between the two groups. We concluded that Old subjects demonstrate a systematic lower muscle oxygen saturation than Young ones. This difference could be explained by an age related decrease in muscle blood flow limiting O(2) supply.     

Non-invasive near infrared spectroscopy of brain in fluorocarbon exchange-transfused rats

Near infrared spectra (700-930 nm) were recorded from the head of anesthetized rats before and after blood substitution with a fluorocarbon emulsion. A large band, centered at 850 nm and characteristic of oxidized cytochrome a, a3, was evidenced in hemoglobin-free living animals. Variations in the amplitude of this absorption band were observed under different respiratory conditions.     

Probing conformational changes of proteins by quantitative second-derivative infrared spectroscopy

Probing protein conformational changes plays a crucial role in protein structure and function studies. However, the lack of efficient biophysical techniques makes it difficult to obtain the distinct behaviors of different secondary structure elements in a protein upon perturbation. This paper presents a discussion of the two major problems, the effect of sidelobes and different half-width at half-height (HWHH) values, encountered in quantitative second-derivative infrared (QSD-IR) spectroscopy and introduces the development of two criteria for checking the validity of the results obtained using the QSD-IR method. It was found that neither the sidelobes nor the HWHH significantly affected the quantitative result of protein conformational changes by using poly-l-lysine and hemoglobin as model proteins. A case study of bovine serum albumin (BSA) thermal aggregation suggested that the thermal transition of BSA was a process involving sequential events, and the two helical components were found to have a distinct response to heat perturbation. These results were confirmed by two-dimensional infrared correlation spectroscopy and by results in literature, suggesting that the QSD-IR method might be a potentially powerful tool to probe the distinct response of different secondary structures to perturbation.     

Measurement of cerebral blood volume using near-infrared spectroscopy and indocyanine green elimination.

Methods for measuring cerebral blood volume (CBV) have traditionally used radioisotopes. More recently, near-infrared spectroscopy (NIRS) has been used to measure CBV by using a technique involving O(2) desaturation of cerebral tissue, where the observed change in the concentration of oxygenated hemoglobin is a marker of the volume of blood contained within the brain. A new integration method employing NIRS is described by using indocyanine green (ICG) as the intravascular marker. After bolus injection, concentration-time integrals of cerebral tissue ICG concentration ([ICG](tissue)) measured by NIRS are compared with corresponding integrals of the cerebral blood ICG concentrations ([ICG](blood)) estimated by high-performance liquid chromatography of peripheral blood samples with allowance for cerebral-to-large-vessel hematocrit ratio. It is shown that CBV = integral [ICG]tissue/[ICG]blood. Measurements in 10 adult volunteers gave a mean value of 1.1 +/- 0.39 (SD) ml/100 g illuminated tissue. This result, although lower than previous NIRS estimations, is consistent with the long extracerebral path of light in the adult head. Scaling of results is required to take into account this component of the optical pathlength.     

Quantitation of drug content in a low dosage formulation by transmission near infrared spectroscopy

A transmission near infrared (NIR) spectroscopic method has been developed for the nondestructive determination of drug content in tablets with less than 1% weight of active ingredient per weight of formulation (m/m) drug content. Tablets were manufactured with drug concentrations of ∼0.5%, 0.7%, and 1.0% (m/m) and ranging in drug content from 0.71 to 2.51 mg per tablet. Transmission NIR spectra were obtained for 110 tablets that constituted the training set for the calibration model developed with partial least squares regression. The reference method for the calibration model was a validated UV spectrophotometric method. Several data preprocessing methods were used to reduce the effect of scattering on the NIR spectra and base the calibration model on spectral changes related to the drug concentration changes. The final calibration model included the spectral range from 11 216 to 8662 cm⁻¹ the standard normal variate (SNV), and first derivative spectral pretreatments. This model was used to predict an independent set of 48 tablets with a root mean standard error of prediction (RMSEP) of 0.14 mg, and a bias of only −0.05 mg per tablet. The study showed that transmission NIR spectroscopy is a viable alternative for nondestructive testing of low drug content tablets, available for the analysis of large numbers of tablets during process development and as a tool to detect drug agglomeration and evaluate process improvement efforts. Published: March 24, 2006     

Investigation of the source‐detector separation in near infrared spectroscopy for healthy and clinical applications

Understanding near infrared light propagation in tissue is vital for designing next generation optical brain imaging devices. Monte Carlo (MC) simulations provide a controlled mechanism to characterize and evaluate contributions of diverse near infrared spectroscopy (NIRS) sensor configurations and parameters. In this study, we developed a multilayer adult digital head model under both healthy and clinical settings and assessed light‐tissue interaction through MC simulations in terms of partial differential pathlength, mean total optical pathlength, diffuse reflectance, detector light intensity and spatial sensitivity profile of optical measurements. The model incorporated four layers: scalp, skull, cerebrospinal‐fluid and cerebral cortex with and without a customizable lesion for modeling hematoma of different sizes and depths. The effect of source‐detector separation (SDS) on optical measurements' sensitivity to brain tissue was investigated. Results from 1330 separate simulations [(4 lesion volumes × 4 lesion depths for clinical +3 healthy settings) × 7 SDS × 10 simulation = 1330)] each with 100 million photons indicated that selection of SDS is critical to acquire optimal measurements from the brain and recommended SDS to be 25 to 35 mm depending on the wavelengths to obtain optical monitoring of the adult brain function. The findings here can guide the design of future NIRS probes for functional neuroimaging and clinical diagnostic systems.      

Human tibia bone marrow blood perfusion by non-invasive near infrared spectroscopy: a new tool for studies on microgravity

Human tibia bone marrow (BM) and tibialis anterior muscle (TA) perfusion index (PI) was assessed non-invasively by near infrared spectroscopy. A decrease in the postis-chaemic reperfusion capability of the human tibia BM and TA muscle was observed for increasing age i.e., PI increases linearly as a function of age, starting from 30 years, both for BM (0.062 %/year, from -4.185 to -0.967 %/s) and TA muscle (0.046 %/year, from -5.760 to -3.883 %/s). The results define a "normal" baseline and demonstrate the sensitivity of the method to PI changes. The present technique should allow one to investigate physio-pathological effects induced by microgravity on tibia BM blood perfusion.