Tissue Hemoglobin Oxygen Saturation Research Articles

Local alternating heat and cold stimulation affects hemodynamics and oxygenation in fatigued muscle tissue and autonomic nervous activity: a single-arm interventional study

BackgroundLocal alternating heat and cold stimulation as an alternative to contrast bath may cause intermittent vasoconstriction and vasodilation, inducing a vascular pumping effect and consequently promoting increased tissue blood flow and oxygenation. This study aimed to examine the effects of local alternating heat and cold stimulation, using a wearable thermal device, on the hemodynamics of fatigued muscle tissue and autonomic nervous activity.MethodsTwenty healthy individuals experienced fatigue in the periarticular muscles of the shoulder joint due to a typing task. Local alternating heat and cold stimulations were then applied to the upper trapezius muscle. Muscle hardness was measured using a muscle hardness meter, and muscle tissue hemodynamics and oxygenation were evaluated using near-infrared spectroscopy before and after the stimulation. Autonomic nervous activity was also evaluated using heart rate variability.ResultsAlternating heat and cold stimulation decreased muscle hardness of the fatigued trapezius muscle from 1.38 ± 0.15 to 1.31 ± 0.14 N (P < 0.01). The concentration of total hemoglobin in the trapezius muscle tissue increased from − 0.21 ± 1.36 to 2.29 ± 3.42 µmol/l (P < 0.01), and the tissue hemoglobin oxygen saturation also increased from 70.1 ± 5.4 to 71.1 ± 6.0% (P < 0.05). Additionally, the heart rate variability parameter, which is an index of sympathetic nervous activity, increased from 3.82 ± 2.96 to 6.86 ± 3.49 (P < 0.01). A correlation was found between increased tissue hemoglobin oxygen saturation and increased parameters of sympathetic nervous activity (r = 0.50, P < 0.05).ConclusionsLocal alternating heat and cold stimulation affected the hemodynamic response in fatigued muscle tissue and autonomic nervous activity. This stimulation is more efficient than conventional contrast baths in terms of mobility and temperature control and has potential as a new versatile therapeutic intervention for muscle fatigue.Trial registrationUMIN-CTR (UMIN000040087: registered on April 7, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045710. UMIN000040620: registered on June 1, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046359).

The Influence of Extracerebral Tissue on Continuous Wave Near-Infrared Spectroscopy in Adults: A Systematic Review of In Vivo Studies.

Near-infrared spectroscopy (NIRS) is a non-invasive technique for measuring regional tissue haemoglobin (Hb) concentrations and oxygen saturation (rSO2). It may be used to monitor cerebral perfusion and oxygenation in patients at risk of cerebral ischemia or hypoxia, for example, during cardiothoracic or carotid surgery. However, extracerebral tissue (mainly scalp and skull tissue) influences NIRS measurements, and the extent of this influence is not clear. Thus, before more widespread use of NIRS as an intraoperative monitoring modality is warranted, this issue needs to be better understood. We therefore conducted a systematic review of published in vivo studies of the influence of extracerebral tissue on NIRS measurements in the adult population. Studies that used reference techniques for the perfusion of the intra- and extracerebral tissues or that selectively altered the intra- or extracerebral perfusion were included. Thirty-four articles met the inclusion criteria and were of sufficient quality. In 14 articles, Hb concentrations were compared directly with measurements from reference techniques, using correlation coefficients. When the intracerebral perfusion was altered, the correlations between Hb concentrations and intracerebral reference technique measurements ranged between |r| = 0.45-0.88. When the extracerebral perfusion was altered, correlations between Hb concentrations and extracerebral reference technique measurements ranged between |r| = 0.22-0.93. In studies without selective perfusion modification, correlations of Hb with intra- and extracerebral reference technique measurements were generally lower (|r| < 0.52). Five articles studied rSO2. There were varying correlations of rSO2 with both intra- and extracerebral reference technique measurements (intracerebral: |r| = 0.18-0.77, extracerebral: |r| = 0.13-0.81). Regarding study quality, details on the domains, participant selection and flow and timing were often unclear. We conclude that extracerebral tissue indeed influences NIRS measurements, although the evidence (i.e., correlation) for this influence varies considerably across the assessed studies. These results are strongly affected by the study protocols and analysis techniques used. Studies employing multiple protocols and reference techniques for both intra- and extracerebral tissues are therefore needed. To quantitatively compare NIRS with intra- and extracerebral reference techniques, we recommend applying a complete regression analysis. The current uncertainty regarding the influence of extracerebral tissue remains a hurdle in the clinical implementation of NIRS for intraoperative monitoring. The protocol was pre-registered in PROSPERO (CRD42020199053).

Tissue Oxygenation Measurement in Patients with Sepsis Compared to the Lactate Levels and Hemodynamical Monitoring

&#x0D; &#x0D; &#x0D; Near-infrared spectroscopy (NIRS) is a noninvasive method for measuring tissue oxygenation. The method allows for monitoring tissue perfusion in shock by revealing tissue hemoglobin oxygen saturation (StO2). The current study aims to compare tissue oxygenation levels with hemodynamical monitoring and lactate levels in patients in severe shock. Study encompasses 19 patients treated in intensive care unit (ICU) at Alexandrovska University Hospital. Ten of the patients cover the criteria for severe sepsis, the remaining nine patients have no data for septic condition. In both groups of patients tissue oxygenation levels measured with INVIOS monitor, mean arterial pressure (MAP), oxygen saturation in mixed venous blood (SvO2) and lactate levels within 72 h of intensive care unit admission are compared. The patients with severe sepsis have significantly lower levels of StO2 in comparison with patients without sepsis. Tissue oxygenation levels correspond to the mean arterial pressure levels, oxygen saturation in mixed venous blood. StO2 levels in the current study do not correlate significantly with the lactate levels in patients with sepsis. Near-infrared spectroscopy as StO2 levels correlate with the hemodynamical monitoring in patients with severe sepsis, but do not correlate significantly with the severity of the disease. This data might indicate that tissue oxygenation monitoring has clinical significance in patients with sepsis. Further profound studies are necessary for assessing the role of tissue oxygenation monitoring in the early phase of resuscitation in septic patients.&#x0D; &#x0D; &#x0D;

Using near-infrared spectroscopy myocardial oximetry to monitor myocardial oxygen balance in a swine model of cardiac surgery: a descriptive study.

Monitoring of the adequacy of myocardial protection with cardioplegia is nearly non-existent in clinical cardiac surgical practice and instead relies on well-defined protocols for delivery of cardioplegia often resulting in inadequate protection. We hypothesized that Near Infrared Spectroscopy technology could be useful in the monitoring of the myocardial oxygen state by attaching the monitors to the epicardium in a porcine model of cardiac surgery. The experiments were conducted with 3 different protocols of 2 pigs each for a total of 6 pigs. The objective was to induce episodic, oxygen supply-demand mismatch. Methods for decreased supply included decreasing coronary blood flow, coronary blood hypoxemia, coronary occlusion, hypovolemia, and hypotension. Methods for increase demand included rapid ventricular pacing and the administration of isoproterenol. Changes in myocardial tissue oximetry were measured and this measurement was then correlated with blood hemoglobin saturations of oxygen from coronary sinus blood samples. We found that decreases in myocardial oxygen supply or increases in demand due to any of the various experimental conditions led to decreases in both myocardial tissue oximetry and hemoglobin oxygen saturation of coronary sinus blood with recovery when the conditions were returned to baseline. Correlation between myocardial tissue oximetry and hemoglobin oxygen saturation of coronary sinus blood was moderate to strong under all tested conditions. This may have translational applications as a monitor of adequacy of myocardial protection and the detection of coronary occlusion.

Can End-tidal Carbon Dioxide Levels Be Used for Determining Tissue Oxygen Saturation in Smokers and Nonsmokers?

Objectives: End-tidal carbon dioxide (EtCO2) monitoring has been used in a range areas, such as invasive sedation procedures, during cardiopulmonary resuscitation, ventilation monitoring of patients with altered mental status, trauma and respiratory system diseases in emergency departments. Near-infrared spectroscopy (NIRS) allows continuous, noninvasive measurement of tissue hemoglobin oxygen saturation (StO2) in muscle and has been studied for a wide range of conditions. In this study we aim to determine the levels of EtCO2 and StO2 in smokers and nonsmokers and the relationship between these two parameters. Methods: We examined 201 healthy volunteers including 156 smokers and 45 nonsmokers. We measured thenar muscle StO2 via NIRS device. The EtCO2 was determined by a capnograph. Baseline measurements were obtained from all participants after not-smoking for two h. Second measurements were taken 5 min after smoking was finished. Results: The mean baseline EtCO2 of the smoker group was 42.61±4,94 (min:31, max:54) mmHg and mean baseline StO2 for this group was 77.81±4.71% (min:69, max:86). In smokers, mean baseline EtCO2 (p:0.00), baseline StO2 (p:0.001), fifth min EtCO2 (p:0.00), fifth min StO2 (p:0.02) levels, and pack*year (p:0.00) were significantly different between males and females. In nonsmokers baseline EtCO2 and baseline StO2 levels were correlated (p:0.035,r:0.315). But we couldn’t find significance between females and males for mean baseline EtCO2 (p:0,246) and baseline StO2 (p:0.264) levels in this group. Conclusion: Smoking affects tissue oxygenation. In nonsmokers baseline EtCO2 and baseline STO2 levels were correlated, but there was no correlation for these two parameters in smokers. Clinicians may use EtCO2 levels for predicting the tissue oxygenation in nonsmoker patients.

Comparison of Frequency- and Time-Domain Autoregulation and Vasoreactivity Indices in a Piglet Model of Hypoxia-Ischemia and Hypothermia

Introduction: The optimal method to detect impairments in cerebrovascular pressure autoregulation in neonates with hypoxic-ischemic encephalopathy (HIE) is unclear. Improving autoregulation monitoring methods would significantly advance neonatal neurocritical care. Methods: We tested several mathematical algorithms from the frequency and time domains in a piglet model of HIE, hypothermia, and hypotension. We used laser Doppler flowmetry and induced hypotension to delineate the gold standard lower limit of autoregulation (LLA). Receiver operating characteristics curve analyses were used to determine which indices could distinguish blood pressure above the LLA from that below the LLA in each piglet. Results: Phase calculation in the frequency band with maximum coherence, as well as the correlation between mean arterial pressure (MAP) and near-infrared spectroscopy relative total tissue hemoglobin (HbT) or regional oxygen saturation (rSO₂), accurately discriminated functional from dysfunctional autoregulation. Neither hypoxia-ischemia nor hypothermia affected the accuracy of these indices. Coherence alone and gain had low diagnostic value relative to phase and correlation. Conclusion: Our findings indicate that phase shift is the most accurate component of autoregulation monitoring in the developing brain, and it can be measured using correlation or by calculating phase when coherence is maximal. Phase and correlation autoregulation indices from MAP and rSO₂ and vasoreactivity indices from MAP and HbT are accurate metrics that are suitable for clinical HIE studies.

Microvascular reactivity, assessed by near-infrared spectroscopy and a vascular occlusion test, is associated with patient outcomes following cardiac surgery: A prospective observational study.

Microvascular dysfunction in patients admitted to the ICU following cardiac surgery may be related to perioperative complications and increased resource utilisation even in the presence of acceptable systemic haemodynamic variables. To assess the relationship between microvascular impairment using peripheral near-infrared spectroscopy at ICU admission and 6 h postadmission and the duration of mechanical ventilatory support, length of stay in ICU and in hospital. Prospective, observational cohort study. Single-centre, tertiary-level cardiac ICU. Sixty-nine adult patients following elective cardiac surgery excluding patients with on-going extracorporeal support or in whom tissue haemoglobin oxygen saturation (StO2) measurements were not feasible. Thenar and forearm StO2 in response to a vascular occlusion test to calculate desaturation and reperfusion slopes. A logistic regression model was used to ascertain the associations between StO2, desaturation and reperfusion slopes as well as cardiac index, mean arterial pressure, arterial lactate concentrations and prolonged (≥75th percentile) duration of mechanical ventilation, ICU length of stay and hospital length of stay. A reduced reperfusion slope at ICU admission was associated independently with prolonged mechanical ventilation at thenar (OR 0.08; 95% CI [0.02 to 0.47], P = 0.003) and forearm [OR 0.2 (0.04 to 0.59), P = 0.006] sites. Similarly, a reduced Rres was associated with prolonged ICU LOS at both thenar [OR 0.3 (0.13 to 0.77), P = 0.007] and forearm [OR 0.2 (0.05 to 0.62), P = 0.007] sites at ICU0 h, as well as ICU6 h [OR 0.2 (0.05 to 0.66), P = 0.004 and OR 0.05 (0.008 to 0.34), P = 0.002]. An increased Rdes was associated with prolonged hospital LOS at the thenar eminence at ICU0 h [OR 1.9 (1.4 to 2.3), P = 0.004] and ICU6 h [OR 6.7 (2.0 to 23), P = 0.002] as well as the forearm at ICU0 h [OR 1.5 (1.3 to 1.9), P = 0.004] and ICU6 h [OR 1.6 (1.3 to 2.1), P = 0.004]. In the early postoperative period following cardiac surgery, changes in thenar and forearm tissue oxygenation variables are associated with patient resource utilisation outcomes.

Near-Infrared Spectroscopy and Vascular Occlusion Test for Predicting Clinical Outcome in Pediatric Cardiac Patients: A Prospective Observational Study.

This study is designed to determine the feasibility and utility of vascular occlusion test variables as measured by INVOS Medtronic, Dublin, Ireland) in pediatric cardiac patients. A prospective observational study. A tertiary children's hospital. Children less than or equal to 8 years old who were scheduled for elective cardiac surgery under cardiopulmonary bypass. A vascular occlusion test (3 min of ischemia and reperfusion) was performed on the calf at three time points: after induction of anesthesia (T0), during cardiopulmonary bypass (T1), and after sternal closure (T2). Baseline regional tissue hemoglobin oxygen saturation, deoxygenation rate, minimum regional tissue hemoglobin oxygen saturation, and reoxygenation rate were measured using INVOS. Influence of age on variables at each measurement point was also checked using linear regression analysis. Receiver operating characteristics curve analysis was performed to determine the ability of vascular occlusion test variables at T2 to predict the occurrence of major adverse events. Both the deoxygenation and reoxygenation rates were lowest in T1. There was a tendency to decreased regional tissue hemoglobin oxygen saturation in younger patients at T0 (r = 0.37; p < 0.001), T1 (r = 0.33; p < 0.001), and T2 (r = 0.42; p < 0.001) during vascular occlusion. Minimum regional tissue hemoglobin oxygen saturation was correlated with age at T0 (r = 0.51; p < 0.001) and T2 (r = 0.35; p = 0.001). Patients with major adverse events had similar baseline regional tissue hemoglobin oxygen saturation but lower minimum regional tissue hemoglobin oxygen saturation (48.8% ± 19.3% vs 63.3% ± 13.9%; p < 0.001) and higher reoxygenation rate (4.30 ± 3.20 vs 2.57 ± 2.39 %/s; p = 0.008) at T2 compared with those without. The minimum regional tissue hemoglobin oxygen saturation less than 51% after sternal closure could predict the occurrence of major adverse events with a sensitivity of 61.1% and a specificity of 85.4%. Vascular occlusion test using INVOS can be applied in children undergoing cardiac surgery. Vascular occlusion test variables are influenced by age and cardiopulmonary bypass. The minimum regional tissue hemoglobin oxygen saturation less than 51% after sternal closure is associated with worse clinical outcomes in pediatric cardiac patients.

Broadband near-infrared spectroscopy can detect cyanide-induced cytochrome aa3 inhibition in rats: a proof of concept study.

Clinically available near-infrared spectroscopy (NIRS) devices use two to five wavelengths of light to measure the relative amounts of oxyhemoglobin and deoxyhemoglobin in tissue to determine tissue hemoglobin oxygen saturation (StO2). In addition to StO2, broadband NIRS devices (using hundreds of wavelengths of light) may be able to measure the oxidation state of mitochondrial cytochrome aa3 (Cytox) which reflects the subcellular energetic state. We hypothesize that broadband NIRS devices can measure Cytox independent of changes in hemoglobin saturation. In this prospective non-randomized study, 20 male Sprague-Dawley rats (300 g) were anesthetized with isoflurane, tracheally intubated, and ventilated with 100% O2 containing 2% isoflurane. They were subsequently instrumented with a broadband NIRS device that used a halogen light source coupled to an emitting fibreoptic cable. Three receiving fibreoptic cables were utilized; one analyzed the light source and the other two were directed at the base of the skull. Each receiving fibre was connected to a spectrometer to measure light intensity. Sodium cyanide (NaCN) 5 mg·kg-1 iv was injected in order to produce cytochrome aa3 reduction. Two to three minutes after injection, oxygen was eliminated and 100% nitrogen (i.e., anoxia) was used for ventilation in order to induce a reduction in both cytochrome aa3 and hemoglobin desaturation. Changes in the cytochrome oxidation state and hemoglobin oxygenation were calculated using a broadband algorithm and compared before and after both the NaCN and anoxia interventions. The NaCN injection resulted in a decrease in median [interquartile range (IQR)] deoxyhemoglobin (-0.014 [-0.29 to -0.005] arbitrary units [AU]; P < 0.001), an increase in oxyhemoglobin (0.013 [-0.011 to 0.031] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.015 [-0.020 to -0.011] AU; P < 0.001). Anoxia resulted in an increase in median [IQR] deoxyhemoglobin (0.13 [0.11 to 0.18] AU; P < 0.001), a decrease in oxyhemoglobin (-0.17 [-0.22 to -0.15] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.04 [-0.06 to -0.03] AU; P < 0.001). Broadband NIRS can effectively measure the directionality of changes in both Cytox and StO2 by uncoupling the cytochrome and hemoglobin signals through inhibition of the electron transport chain and anoxia.

The impact of red blood cell storage duration on tissue oxygenation in cardiac surgery

ObjectiveAlthough storage alters red blood cells, several recent, randomized trials found no differences in clinical outcomes between patients transfused with red blood cells stored for shorter versus longer periods of time. The objective of this study was to see whether storage impairs the in vivo ability of erythrocytes to traverse the microcirculation and deliver oxygen at the tissue level. MethodsA subset of subjects from a clinical trial of cardiac surgery patients randomized to receive transfusions of red blood cells stored ≤10 days or ≥21 days were assessed for thenar eminence and cerebral tissue hemoglobin oxygen saturation (StO2) via the use of near-infrared spectroscopy and sublingual microvascular blood flow via side-stream darkfield videomicroscopy. ResultsAmong 55 subjects, there was little change in the primary endpoint (thenar eminence StO2 from before to after transfusion of one unit) and the change was similar in the 2 groups: +1.7% (95% confidence interval, −0.3, 3.8) for shorter-storage and +0.8% (95% confidence interval, −1.1, 2.9) for longer-storage; P = .61). Similarly, no significant differences were observed for cerebral StO2 or sublingual microvascular blood flow. These parameters also were not different from preoperatively to 1 day postoperatively, reflecting the absence of a cumulative effect of all red blood cell units transfused during this period. ConclusionsThere were no differences in thenar eminence or cerebral StO2, or sublingual microcirculatory blood flow, in cardiac surgery patients transfused with red blood cells stored ≤10 days or ≥21 days. These results are consistent with the clinical outcomes in the parent study, which also did not differ, indicating that storage may not impair oxygen delivery by red blood cells in this setting.

Can transcutaneous near infrared spectroscopy detect severe hepatic ischemia: a juvenile porcine model.

Vascular complications following pediatric liver transplantation occur in 8-10% of cases, and no continuous, non-invasive monitoring for this problem exists. Near infrared spectroscopy (NIRS) allows non-invasive, continuous, transcutaneous assessment of hemoglobin oxygenation (StO2 ) 1-4 cm below the skin surface. We hypothesized that transcutaneous NIRS would be able to detect severe hepatic ischemia, and tested this in an animal model using 15-20 kg and 5-7 kg juvenile pigs. Direct liver surface and transcutaneous hepatic tissue hemoglobin oxygen saturation (StO2 ) were measured during occlusions of the hepatic artery and portal vein. Changes in hepatic delivery of oxygen (HepDO2 ) were calculated for each ischemic challenge and compared to changes in direct liver surface (DirHepStO2 ) and transcutaneous liver StO2 measurements (CutHepStO2 ). In the 15-20 kg animals during complete occlusion, CutHepStO2 decreased by 6.0(±4.9)%, whilst DirHepStO2 decreased by 83.7(±7.2)%. In the 5-7 kg animals during complete occlusion, CutHepStO2 decreased by 27.4(±8.5)%, whilst DirHepStO2 decreased by 82.8(±4.6)%. Transcutaneous hepatic StO2 monitoring cannot reliably detect severe hepatic ischemia in a juvenile porcine model, although a stronger and potentially useful signal is seen in 5-7 kg pigs. Trials of this technology should be currently restricted to situations where the organ is less than 1 cm from the skin surface, corresponding to infants of <10 kg.

Skeletal muscle oxygenation in severe trauma patients during haemorrhagic shock resuscitation.

IntroductionEarly alterations in tissue oxygenation may worsen patient outcome following traumatic haemorrhagic shock. We hypothesized that muscle oxygenation measured using near-infrared spectroscopy (NIRS) on admission could be associated with subsequent change in the SOFA score after resuscitation.MethodsThe study was conducted in two Level I trauma centres and included 54 consecutive trauma patients with haemorrhagic shock, presenting within 6 hours of injury. Baseline tissue haemoglobin oxygen saturation (StO2) in the thenar eminence muscle and StO2 changes during a vascular occlusion test (VOT) were determined at 6 hours (H6) and 72 hours (H72) after the admission to the emergency room. Patients showing an improved SOFA score at H72 (SOFA improvers) were compared to those for whom it was unchanged or worse (SOFA non-improvers).ResultsOf the 54 patients, 34 patients were SOFA improvers and 20 SOFA non-improvers. They had comparable injury severity scores on admission. SOFA improvers had higher baseline StO2 values and a steeper StO2 desaturation slope at H6 compared to the SOFA non-improvers. These StO2 variables similarly correlated with the intra-hospital mortality. The StO2 reperfusion slope at H6 was similar between the two groups of patients.ConclusionsDifferences in StO2 parameters on admission of traumatic haemorrhagic shock were found between patients who had an improvement in organ failure in the first 72 hours and those who had unchanged or worse conditions. The use of NIRS to guide the initial management of trauma patients with haemorrhagic shock warrants further investigations.

Assessment of Microcirculatory Hemoglobin Levels in Normal and Diabetic Subjects using Diffuse Reflectance Spectroscopy in the Visible Region — a Pilot Study

Light-based diagnostic techniques provide a minimally invasive way for selective biomarker estimation when tissues transform from a normal to a malignant state. Spectroscopic techniques based on diffuse reflectance characterize the changes in tissue hemoglobin/oxygenation levels during the tissue transformation process. Recent clinical investigations have shown that changes in tissue oxygenation and microcirculation are observed in diabetic subjects in the initial and progressive stages. In this pilot study, we discuss the potential of diffuse reflectance spectroscopy (DRS) in the visible (Vis) range to differentiate the skin microcirculatory hemoglobin levels between normal and advanced diabetic subjects with and without neuropathy. Average concentration of hemoglobin as well as hemoglobin oxygen saturation within the probed tissue volume is estimated for a total of four different sites in the foot sole. The results indicate a statistically significant decrease in average total hemoglobin and increase in hemoglobin oxygen saturation levels for diabetic foot compared with a normal foot. The present study demonstrates the ability of reflectance spectroscopy in the Vis range to determine and differentiate the changes in tissue hemoglobin and hemoglobin oxygen saturation levels in normal and diabetic subjects.

Novel, Noninvasive Multispectral Snapshot Imaging System to Measure and Map the Distribution of Human Retinal Vessel and Tissue Hemoglobin Oxygen Saturation

Novel, Noninvasive Multispectral Snapshot Imaging System to Measure and Map the Distribution of Human Retinal Vessel and Tissue Hemoglobin Oxygen Saturation

Challenges and Possibilities in Forward Resuscitation

The environmental and logistical constraints of the prehospital setting make it a challenging place for the treatment of trauma patients. This is perhaps more pronounced in the management of battlefield casualties before extraction to definitive care. In seeking solutions, interest has been renewed in implementing damage control resuscitation principles in the prehospital setting, a concept termed remote damage control resuscitation. These developments, while improving conflict survival rates, are not exclusive to the military environment, with similar situations existing in the civilian setting. By understanding the pathophysiology of shock, particularly the need for oxygen debt repayment, improvements in the assessment and management of trauma patients can be made. Technology gaps have previously hampered our ability to accurately monitor the prehospital trauma patient in real time. However, this is changing, with devices such as tissue hemoglobin oxygen saturation monitors and point-of-care lactate analysis currently being refined. Other monitoring modalities including newer signal analysis and artificial intelligence techniques are also in development. Advances in hemostatic resuscitation are being made as our understanding and ability to effectively monitor patients improve. The reevaluation of whole-blood use in the prehospital environment is yielding favorable results and challenging the negative dogma currently associated with its use. Management of trauma-related airway and respiratory compromise is evolving, with scope to improve on currently accepted practices. The purpose of this review is to highlight the challenges of treating patients in the prehospital setting and suggest potential solutions. In doing so, we hope to maintain the enthusiasm from people in the field and highlight areas for prehospital specific research and development, so that improved rates of casualty survival will continue.

Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection

A rapid heuristic ratiometric analysis for estimating tissue hemoglobin concentration and oxygen saturation from measured tissue diffuse reflectance spectra is presented. The analysis was validated in tissue-mimicking phantoms and applied to clinical measurements in head and neck, cervical and breast tissues. The analysis works in two steps. First, a linear equation that translates the ratio of the diffuse reflectance at 584 nm and 545 nm to estimate the tissue hemoglobin concentration using a Monte Carlo-based lookup table was developed. This equation is independent of tissue scattering and oxygen saturation. Second, the oxygen saturation was estimated using non-linear logistic equations that translate the ratio of the diffuse reflectance spectra at 539 nm to 545 nm into the tissue oxygen saturation. Correlations coefficients of 0.89 (0.86), 0.77 (0.71) and 0.69 (0.43) were obtained for the tissue hemoglobin concentration (oxygen saturation) values extracted using the full spectral Monte Carlo and the ratiometric analysis, for clinical measurements in head and neck, breast and cervical tissues, respectively. The ratiometric analysis was more than 4000 times faster than the inverse Monte Carlo analysis for estimating tissue hemoglobin concentration and oxygen saturation in simulated phantom experiments. In addition, the discriminatory power of the two analyses was similar. These results show the potential of such empirical tools to rapidly estimate tissue hemoglobin in real-time spectral imaging applications.

Abstract P2-03-09: Tissue hemoglobin oxygen saturation measured by photoacoustic mammography correlates with microvasculature properties assessed by histological image analysis, a preliminary study

Abstract Background: Photoacoustic mammography (PAM) is a new optical imaging technology with the potential of imaging tumor vasculature in breast cancer.The technique is applicable to the measurement of hemoglobin oxygen saturation (SO2).We have previously published an initial clinical result using a prototype machine (Canon Inc.,Tokyo, Japan) in breast cancer. We have also presented the morphological characteristics of tumor vessels analyzed by automated image processing during AACR annual meeting 2013. Here, we report the oxygenation data obtained by PAM in relation with histological assessment of tumor vasculature and hypoxia. Methods: Forty-four breast lesions were evaluated by PAM in this IRB approved prospective study at Kyoto University Hospital, Japan. PAM evaluation was performed on both breasts whenever possible.SO2 was calculated in region of interest after the radiologist confirmed the signal was associated with the tumor location in MRI images. For the normal breast, signals obtained at the same depth of the tumor, were selected. Eighty-one histological sections from 20 available invasive carcinoma tissues at the time of this analysis were selected for immunohistochemical assessment of hypoxia by anti -carbonic anhydrase IX (CA IX) and tumor vasculature image analysis using anti-CD31. Five 0.5 mm2 area of each cancer and 3 area of normal mammary tissue associated with the same lesion were randomly selected from different sections. Total vascular area in each square was calculated by using Image Pro-Plus 7.0 software (Media Cybernetics, USA). Tumor-to-normal vascular area ratio (T/N VA) was calculated for each lesion as an index for tumor blood supply. Results: Patients’ age ranged from 36 to 83 years old. Tumor associated signals were detected by PAM in 18 out of 20 lesions for which tissues were available for histological examination. SO2 in tumor was calculated 70.6% ±13.2 and 83.3% ±10.7 in the normal counterpart. While T/N VA ranged between 0.11 to 1.14, it was almost 3 times lower in lesions with CA IX positive cytoplasmic membrane staining (0.21 vs 0.7, p-value = 0.021 Mann-Whitney Test). Normalized tumor SO2 (tumor SO2/normal counterpart SO2) was significantly lower in the group with lower T/N VA (0.9 vs. 0.8,p-value = 0.045, Student T-test). To better evaluate the accuracy of PAM measurement in calculating SO2,3780 tumor-associated and 2835 normal microvessels were analyzed by image analysis software. Tumor associated vessels had significantly smaller area (p-value&amp;lt;0.001) and vessels with irregular lumens were more frequent in tumor (76.5% vs 19.6% p-value &amp;lt;0.001) compatible with lower SO2 in tumor areas. Conclusion: Although the future result of our ongoing clinical studies of PAM measurement in breast cancer patients are more than necessary, the strong correlation between histological evaluation of hypoxia and angiogenesis with PAM measurement of oxygenation shows the promising prospective for clinical application of this new technology in breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-03-09.

Hemodynamic signature of breast cancer under fractional mammographic compression using a dynamic diffuse optical tomography system

Near infrared dynamic diffuse optical tomography measurements of breast hemodynamics during fractional mammographic compression offer a novel contrast mechanism for detecting breast cancer and monitoring chemotherapy. Tissue viscoelastic relaxation during the compression period leads to a slow reduction in the compression force and reveals biomechanical and metabolic differences between healthy and lesion tissue. We measured both the absolute values and the temporal evolution of hemoglobin concentration during 25-35 N of compression for 22 stage II and III breast cancer patients scheduled to undergo neoadjuvant chemotherapy. 17 patients were included in the group analysis (average tumor size 3.2 cm, range: 1.3-5.7 cm). We observed a statistically significant differential decrease in total and oxy-hemoglobin, as well as in hemoglobin oxygen saturation in tumor areas vs. healthy tissue, as early as 30 seconds into the compression period. The hemodynamic contrast is likely driven by the higher tumor stiffness and different viscoelastic relaxation rate, as well as the higher tumor oxygen metabolism rate.

Type 2 diabetes mellitus and exercise impairment

Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study.

Effects of Compression on Muscle Tissue Oxygenation at the Onset of Exercise

The effects of compression on gastrocnemius medialis muscle oxygenation and hemodynamics during a short-term dynamic exercise was investigated in a sample of 15 male subjects (mean ± SD; age 25.8 ± 4.9 years; mass 70.6 ± 4.3 kg). Elastic compression sleeves were used to apply multiple levels of compression to the calf muscles during exercise, and noncompressive garments were used for the control condition. Tissue hemoglobin oxygen saturation was measured as the relative "tissue oxygen index" (TOI) with a near-infrared spectrometer. The recovery of TOI during exercise was determined from the slope of oxygenation recovery in a nonoccluded situation. The TOI recovery rate during the first 2 minutes of the exercise was 24% higher (p = 0.042) for the compression condition than for the control condition. A significant correlation (r = 0.61, p = 0.012) between the level of compression and the tissue oxygenation recovery during exercise was observed. Muscle energy use was determined from the rate of decline of TOI immediately upon arterial occlusion during early exercise. Muscle energy use measured during the occluded situation was not significantly influenced by compression. Based on these results, it was concluded that compression induced changes in tissue blood flow and perfusion appear to result in improved oxygenation during short-term exercise. Assuming that increased muscle oxygen availability positively influences performance, compression of muscles may enhance performance especially in sports that require repeated short bouts of exercise.