NIR spectroscopic detection of breast cancer.

Near infrared spectroscopy (NIRS) utilizes intrinsic optical absorption signals of blood, water, and lipid concentration available in the NIR window (600-1000 nm) as well as a developing array of extrinsic organic compounds to detect and localize cancer. This paper reviews optical cancer detection made possible through high tumor-tissue signal-to-noise ratio (SNR) and providing biochemical and physiological data in addition to those obtained via other methods. NIRS detects cancers in vivo through a combination of blood volume and oxygenation from measurements of oxy- and deoxy-hemoglobin giving signals of tumor angiogenesis and hypermetabolism. The Chance lab tends towards CW breast cancer systems using manually scannable detectors with calibrated low pressure tissue contact. These systems calculate angiogenesis and hypermetabolism by using a pair of wavelengths and referencing the mirror image position of the contralateral breast to achieve high ROC/AUC. Time domain and frequency domain spectroscopy were also used to study similar intrinsic breast tumor characteristics such as high blood volume. Other NIRS metrics are water-fat ratio and the optical scattering coefficient. An extrinsic FDA approved dye, ICG, has been used to measure blood pooling with extravasation, similar to Gadolinium in MRI. A key future development in NIRS will be new Molecular Beacons targeting cancers and fluorescing in the NIR window to enhance in vivo tumor-tissue ratios and to afford biochemical specificity with the potential for effective photodynamic anti-cancer therapies.

Oxygen transport and intracellular bioenergetics on stimulated cat skeletal muscle.

A unique multiparameter recording of skeletal muscle bioenergetics, biochemistry and biomechanics has permitted determination of novel relationships among hemodynamics, cellular high-energy metabolites and mitochondrial bioenergetics in feline skeletal muscle. The study utilizes 31P NMR, NIR, and NADH fluorescence spectrophotometry, biochemical assays and muscle performance. Seven cats were anesthetized and mechanically ventilated. Calf muscles were stimulated through sciatic nerve electrical stimulation and tension was monitored by a strain gauge connected to the Achilles tendon. We stimulated the muscle to produce several workloads up to Vmax. We also changed FiO2 from normoxia to hypoxia for each %Vmax. From these results, the most sensitive indicators of cellular hypoxia leading to a reduction in muscle performance can be determined. Hemoglobin deoxygenation generally does not correlate with cellular hypoxia, although when the HbO2 drops below 30% saturation there is an increased incidence of cellular hypoxia. The [ADP], which is known to regulate mitochondrial function, has a close relation to the work, not to the hypoxia. On the other hand, the mitochondrial NADH does respond to cellular PO2. The degree of oxidation (NADH decrease) due to the ATP flux shifts with oxygen availability in mild to moderate hypoxia (at FiO2 down to 9%). As cellular hypoxia causes decreases in muscle performance (moderate to severe hypoxia), NADH is being reduced rather than oxidized with increasing workloads.

Regional difference of muscle oxygen saturation and blood volume during exercise determined by near infrared imaging device.

UNLABELLED: Using a near infrared (NIR) imaging device, we tested the hypothesis that regional differences in oxygen status could be detected in the gastrocnemius muscle during exercise and recovery. Six healthy subjects performed the standing plantar flexion exercises for 2 min; the frequency was one contraction per second. The NIR imaging device was placed over the medial head of the right gastrocnemius muscle and the signals from two optical sensors situated on the middle proximal and middle distal portions were used. The NIR-O(2) saturation (difference between deoxygenated and oxygenated Hb signals) and NIR-blood volume (sum of the oxygenated and deoxygenated Hb signals) were calculated in optical density units. Plantar flexion resulted in more deoxygenation during exercise and more reoxygenation during recovery in the distal portion compared with the proximal portion. The changes in NIR-O(2) between rest and a 2 min exercise, and between a 2 min exercise and a 3 min recovery were 0.11 and -0.23, respectively, in the distal portion, which were significantly larger than proximal values (0.05 and -0.10, p < 0.05). Plantar flexion resulted in lower NIR-blood volumes during exercise and greater recovery of blood after exercise in the distal portion compared with the proximal portion. The changes in NIR blood volume between rest and a 2 min exercise and between a 2 min exercise and a 3 min recovery were -0.19 and 0.31, respectively, in the distal portion, significantly larger than proximal values (-0.07 and 0.12, p < 0.05 for all comparisons). These findings indicate that the distal portion of the medial gastrocnemius had larger changes in NIR-O(2) saturation and NIR-blood volume than the proximal portion had. This is consistent with the distal portion having a greater impairment of blood flow possibly because of the higher intramuscular pressure during exercise. IN CONCLUSION: (1) regional differences in oxygen status in the gastrocnemius muscle were detected with exercise, with the distal portion having greater NIR-O(2) saturation and NIR-blood volume changes, and (2) the NIR imaging device might be a useful method to detect the regional differences of oxygen status in the muscle.

Muscle oxygen desaturation is related to whole body VO2 during cross-country ski skating.

Previous research has demonstrated that blood flow and subsequent O2 desaturation (OD) in exercising muscle is related to the static component during exercise. In speed skating, increased OD is dissociated from whole body VO2 and heart rate (HR) when the skater increases the static component by 'sitting low'. This phenomenon was evaluated in cross-country skiers by manipulating speed and incline during treadmill roller skiing. Eight male cross-country skiers (22.4 +/- 3.2 yrs old) randomly performed constant incline- and constant speed-based protocols in which increased load was manipulated in five 4min stages by treadmill incline or speed change, respectively. A strong relationship (r = 0.83) was observed between VO2 and % OD while blood volume change (deltaBV) was minimal. Unexpectedly, no HR/ VO2 or HR/OD shifts were observed between protocols. The % OD response, in relation to blood lactate values, during submaximal exercise was very similar to that of VO2. The lack of an observed greater desaturation at higher inclines suggests that the expected static load may be attenuated by an increased contribution of poling. The strong relationship of % OD to whole body VO2 may be attributed to O2 dissociation in the capillary bed of the muscle to meet aerobic energy demand and is independent of blood flow dynamics during cross-country ski skating.

Hemoglobin/myoglobin oxygen desaturation during Alpine skiing.

PURPOSE: To investigate muscle blood volume (BV) change and hemoglobin/myoglobin oxygen desaturation (OD) during simulated giant slalom (GS) and slalom (SL) Alpine ski racing. METHODS: Joint angle, BV, OD, and heart rate (HR) were evaluated during GS and SL events in 30 junior elite skiers ages 9--17 yr (13.5 +/- 2.3). Subjects were stratified by ski class and age: group I, J1 and J2, ages 15--18 yr (16.8 +/- 0.8); group II, J3, 13--14 yr (13.6 +/- 0.7); and group III, J4 and J5, 9--12 yr (11.5 +/- 1.2). Near-infrared spectrophotometry (NIRS) was used to measure BV and OD in the capillary bed of the vastus lateralis during trials. Maximal OD was determined during thigh cuff ischemia (CI). Quadriceps cross-sectional area (CSA) was estimated by skin-fold and thigh circumference. RESULTS: Joint angles were smaller (P < 0.05) during GS than SL for ankle (83.8 +/- 11.9 degrees; 98.6 +/- 15.7 degrees ), knee (107.4 +/- 14.9 degrees; 118.3 +/- 18.0 degrees ), and hip (98.8 +/- 14.3 degrees; 107.5 +/- 16.2 degrees ). BV reduction from rest to peak exercise (Delta BV) was 30% greater (P < 0.05) during the GS than SL, whereas Delta OD was 33% greater (P < 0.05) during GS. Delta OD, relative to CI OD, was greater for all subjects during GS (79.2 +/- 3.7%) than SL (65.7 +/- 4.4%). This pattern continued within groups; group II displayed the greatest relative desaturation (82.9 +/- 7.6%). CSA was larger in older skiers (92.5 +/- 21.6; 72.5 +/- 12.3; 65.3 +/- 21.2 cm(2)) and correlated with Delta OD (P < 0.05). CONCLUSION: The larger reduction in BV (Delta BV change) and greater OD when skiers assumed lower posture during GS than SL may be related to greater effective static load secondary to higher percent of maximal voluntary contraction and is consistent with compromised blood flow to working muscle.

Preliminary evaluation of dual wavelength phased array imaging on neonatal brain function.

Imaging of human tissue using noninvasive techniques has been of great interest in biomedical fields. Optical imaging has attracted a lot of attention because of its portability and economy. The possibility that a highly portable, fast, safe, and affordable imaging system which could obtain interpretable images of brain function for pre- and full-term neonates in a few seconds, has been explored in this article. We have used a sensitive optical topography system, termed phased array, in which a pair of equal-amplitude and antiphase light sources are applied to generate a sharp amplitude null and phase transition plane. This two-wavelength (750 and 830 nm), frequency encoded (50 and 52 MHz) phased array imaging system can indicate the blood concentration and oxygenation changes in blood model studies and during parietal brain activation in neonates. Significant functional responses, particularly to parietal stimulation in normal and pathological states of neonatal brain, have been revealed in our study. The preliminary clinical results are presented in this article.

Study of near infrared technology for intracranial hematoma detection.

Although intracranial hematoma detection only requires the continuous wave technique of near infrared spectroscopy (NIRS), previous studies have shown that there are still some problems in obtaining very accurate, reliable hematoma detection. Several of the most important limitations of NIR technology for hematoma detection such as the dynamic range of detection, hair absorption, optical contact, layered structure of the head, and depth of detection are reported in this article. A pulsed light source of variable intensity was designed and studied in order to overcome hair absorption and to increase the dynamic range and depth of detection. An adaptive elastic optical probe was made to improve the optical contact and decrease contact noise. A new microcontroller operated portable hematoma detector was developed. Due to the layered structure of the human head, simulation on a layered medium was analyzed experimentally. Model inhomogeneity tests and animal hematoma tests showed the effectiveness of the improved hematoma detector for intracranial hematoma detection.

Muscle deoxygenation in aerobic and anaerobic exercise.

It has been generally accepted that the use of oxygen is a major contributor of ATP synthesis in endurance exercise but not in short sprints. In anaerobic exercise, muscle energy is thought to be initially supported by the PCr-ATP system followed by glycolysis, not through mitochondrial oxidative phosphorylation. However, in real exercise practice, we do not know how much of this notion is true when an athlete approaches his/her maximal capacity of aerobic and anaerobic exercise, such as during a graded VO2max test. This study investigates the use of oxygen in aerobic and anaerobic exercise by monitoring oxygen concentration of the vastus lateralis muscle at maximum intensity using Near Infra-red Spectroscopy (NIRS). We tested 14 sprinters from the University of Penn track team, whose competitive events are high jump, pole vault, 100 m, 200 m, 400 m, and 800 m. The Wingate anaerobic power test was performed on a cycle ergometer with 10% body weight resistance for 30 seconds. To compare oxygenation during aerobic exercise, a steady-state VO2max test with a cycle ergometer was used with 25 watt increments every 2 min. until exhaustion. Results showed that in the Wingate test, total power reached 774 +/- 86 watt, about 3 times greater than that in the VO2max test (270 +/- 43 watt). In the Wingate test, the deoxygenation reached approximately 80% of the established maximum value, while in the VO2max test resulted in approximately 36% deoxygenation. There was no delay in onset of deoxygenation in the Wingate test, while in the VO2max test, deoxygenation did not occur under low intensity work. The results indicate that oxygen was used from the beginning of sprint test, suggesting that the mitochondrial ATP synthesis was triggered after a surprisingly brief exercise duration. One explanation is that prior warm-up (unloaded exercise) was enough to provide the mitochondrial substrates; ADP and Pi to activate oxidative phosphorylation by the type II a and type I myocytes. In addition, transmural pressure created by the muscle contraction reduces blood flow, causing relative hypoxia.

A novel method for fast imaging of brain function, non-invasively, with light.

Imaging of the human body by any non-invasive technique has been an appropriate goal of physics and medicine, and great success has been obtained with both Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) in brain imaging. Non-imaging responses to functional activation using near infrared spectroscopy of brain (fNIR) obtained in 1993 (Chance, et al. [1]) and in 1994 (Tamura, et al. [2]) are now complemented with images of pre-frontal and parietal stimulation in adults and pre-term neonates in this communication (see also [3]). Prior studies used continuous [4], pulsed [3] or modulated [5] light. The amplitude and phase cancellation of optical patterns as demonstrated for single source detector pairs affords remarkable sensitivity of small object detection in model systems [6]. The methods have now been elaborated with multiple source detector combinations (nine sources, four detectors). Using simple back projection algorithms it is now possible to image sensorimotor and cognitive activation of adult and pre- and full-term neonate human brain function in times < 30 sec and with two dimensional resolutions of < 1 cm in two dimensional displays. The method can be used in evaluation of adult and neonatal cerebral dysfunction in a simple, portable and affordable method that does not require immobilization, as contrasted to MRI and PET.

Optical investigations of physiology: a study of intrinsic and extrinsic biomedical contrast.

The utility and performance of optical studies of tissue depends upon the contrast and the changes of contrast in health and disease and in functional activity. The contrast is determined both by the optical properties of extrinsic chromophores and scatterers but especially upon the changes evoked by physiological activity and pathological states. Here, we have focused upon absorption changes of the intrinsic probe, blood absorbance changes due to cortical hypoxia and to haematomas, giving, for particular conditions, absorbance changes of 0.15 and over 0.4 delta OD, respectively. Functional activity may give changes of blood volume of over 0.05 delta OD with some variability due to individual responses that is best expressed as histogram displays of the distribution of response among a significant population. Responses have been observed in prefrontal parietal and occipital functions (242 tests). Extrinsic probes afford signals dependent upon the dose tolerance of the subject and can readily equal or exceed the blood volume and oxygenation signals, and currently afford vascular volume and flow indications. However, contrast agents for the functional activity of cellular function are ultimately to be expected. Finally, light-scattering changes afford osmolyte-related responses and are here shown to indicate a larger signal attributed to cortical depolarization and K+ release in hypoxia/ischaemia. Thus, the optical method affords imaging of manifold contrasts that greatly enhance its specificity and sensitivity for diagnostic procedures.

Hemoglobin/myoglobin desaturation during speed skating.

The characteristic low "sitting" position of competitive speed skating has been shown to result in a right shifted heart rate-VO2 curve and elevated submaximal blood lactate values compared with running or cycling. This is thought to be a consequence of reduced blood flow and subsequent oxygen delivery to the exercising muscle while speed skating. Duel wavelength spectrophotometry was used to measure oxygenated and deoxygenated hemoglobin/myoglobin (OD) in the capillary bed of five muscle groups during in-line skating in upright (US) and low (LS) positions. Eight U.S. speed skaters (4 category 1) performed US and LS at 2.68 and 3.13 m.s-1 (4% grade) on a wide (2.44 m) treadmill (4 trials, 5 min each, 20 min recovery between trials). Expired gas parameters and blood lactate (LA) concentrations were determined for each trial. Hip and knee angles were measured (PEAK Motion Analysis) and were significantly different in US and LS. For similar oxygen uptake during US and LS (44.9 +/- 2.79, 45.6 +/- 3.52), heart rate and LA were significantly higher during LS (172 +/- 11 vs 179 +/- 10, 4.35 +/- 2.19 vs 8.70 +/- 3.60). Deoxygenation was significantly greater during LS than during US at both speeds and was greater at 3.13 m.s-1 (P < 0.05). OD was highly related to LA (r > 0.95) but not to whole body VO2. Blood volume change was less for LS than for US (P < 0.05). Increased deoxygenation in the capillary bed of the exercising quadriceps during LS versus US is consistent with the hypothesis that blood flow and subsequent O2 delivery is compromised in the low speed skating position.

Human brain functional imaging with reflectance CWS.

Continuous Wave Spectroscopy (CWS) has been used in human subjects to detect brain function by observation of brain oxygenation and blood volume changes. In this research, we have developed a device for imaging brain oxygenation and blood volume with multiple sources and detectors in an area of 10 x 12 cm. Twelve, 1 watt tungsten bulbs were used as a light source, together with 8 detectors consisting of silicon-photodiodes with band-pass filters at 760 and 850 nms. The detectors were placed on a model system of the human head, providing 16 source-detector combinations with 4 cm separation. Eight to 16 seconds were required to image a brain function. Models using resin and a black object which have similar optical characteristics to a brain were studied. The model study showed that we can detect changes in absorption as deep as 2 cm from the surface. Human subjects with relatively thin hair, who volunteered for this study, were asked to tap fingers and rest, or to observe light flashing and darkness alternatively for 10 to 20 minutes while the images were being taken. In the finger tapping, the blood volume increased in a small, 1-2 cm area, while in the light stimulation, a much larger area was affected with a greater increased blood volume. Oxygenation occurred also in the area where blood volume increased. We concluded that the CWS can be used to image the location of brain activity by means of blood volume increase and oxygenation. In addition, brain disfunction and diseases, such as learning disability and brain hematoma may be detected with this imaging device.

Oxygenation and blood volume changes in flaps according to near-infrared spectrophotometry.

OBJECTIVE: To test the ability of near-infrared spectrophotometry (NIRS) to predict vascular compromise in flaps postoperatively. DESIGN: Pilot study. SUBJECTS: Eleven denervated latissimus dorsi flaps were assessed in 8 pigs. INTERVENTIONS: Flaps were isolated on their vascular pedicle. We used NIRS to demonstrate tissue oxygen saturation and quantities of deoxygenated hemoglobin and oxygenated hemoglobin when flaps underwent venous or arterial occlusions. Oxygen saturation (percentage of oxygenated hemoglobin) was calculated as the difference between the 2 light intensities (860-750 nm) with the use of 2 time periods: preoperative (80%) oxygen saturation and during arterial occlusion (0%) oxygen saturation with NIRS. Blood volume changes within the flap were also measured. RESULTS: Arterial occlusion resulted in significant decreases in oxygen saturation and in blood volume with immediate recovery. Venous occlusion resulted in an initial rapid increase in blood volume with no appreciable early deoxygenation. CONCLUSIONS: Near-infrared spectrophotometry appears promising as a noninvasive, low-cost, portable bedside monitor that can demonstrate in real time changes in blood volume and oxygen saturation within a flap at a variety of tissue depths.

Seizure susceptibility during recovery from hypercapnia in neonatal dogs.

Seizure susceptibility during recovery from hypercapnia was investigated in seven anesthetized neonatal dogs; 13, 20, or 30% CO2 gas was administered for 30 min through a ventilator to result in three levels of hypercapnia in which measured PaCO2 values were approximately 70, 100, and 140 mm Hg. Thereafter, the animals were allowed to recover for 45 min; during this recovery phase, electrocorticography was performed. In five of seven dogs, approximately 1.5 Hz slow irregular spike and wave bursts appeared at 6 min after abrupt withdrawal from hypercapnia and lasted several minutes. This seizure activity was followed by a brief period of electrical suppression. This phenomenon was most often observed during the recovery from moderate hypercapnia and between the PaCO2 values of 100 and 50 mm Hg. When seizure activities appeared in the electrocorticogram, arterial blood pressure increased -40 mm Hg from the preseizure level. These results suggest that neonatal seizures may occur during recovery from hypercapnia.