Epinephrine iontophoresis attenuates changes in skin blood flow and abolishes cutaneous contamination of near-infrared diffuse correlation spectroscopy estimations of muscle perfusion.

Near-infrared diffuse correlation spectroscopy (NIR-DCS) is an optical imaging technique for measuring relative changes in skeletal muscle microvascular perfusion (i.e., fold change above baseline) during reactive hyperemia testing and exercise and is reported as a blood flow index (BFI). Although it is generally accepted that changes in BFI are primarily driven by changes in muscle perfusion, it is well known that large, hyperthermia-induced changes in cutaneous blood flow can uncouple this relationship. What remains unknown, is how much of an impact that changes in cutaneous perfusion have on NIR-DCS BFI and estimates of skeletal muscle perfusion under thermoneutral conditions, where changes in cutaneous blood flow are assumed to be relatively low. We therefore used epinephrine iontophoresis to pharmacologically block changes in cutaneous perfusion throughout a battery of experimental procedures. The data show that 1) epinephrine iontophoresis attenuates changes in cutaneous perfusion for up to 4-h posttreatment, even in the face of significant neural and local stimuli, 2) under thermoneutral conditions, cutaneous perfusion does not significantly impact NIR-DCS BFI during reactive hyperemia testing or moderate-intensity exercise, and 3) during passive whole body heat stress, when cutaneous vasodilation is pronounced, epinephrine iontophoresis preserves NIR-DCS measures of skeletal muscle BFI during moderate-intensity exercise. Collectively, these data suggest that cutaneous perfusion is unlikely to have a major impact on NIR-DCS estimates of skeletal muscle BFI under thermoneutral conditions, but that epinephrine iontophoresis can be used to abolish cutaneous contamination of the NIR-DCS BFI signal during studies where skin blood flow may be elevated but skeletal muscle perfusion is of specific interest.

Do Cerebral Cortex Perfusion, Oxygen Delivery, and Oxygen Saturation Responses Measured by Near-Infrared Spectroscopy Differ Between Patients Who Fail or Succeed in a Spontaneous Breathing Trial? A Prospective Observational Study.

BACKGROUND: Alterations in perfusion to the brain during the transition from mechanical ventilation (MV) to a spontaneous breathing trial (SBT) remain poorly understood. The aim of the study was to determine whether changes in cerebral cortex perfusion, oxygen delivery (DO2), and oxygen saturation (%StiO2) during the transition from MV to an SBT differ between patients who succeed or fail an SBT. METHODS: This was a single-center prospective observational study conducted in a 16-bed medical intensive care unit of the University Hospital Leuven, Belgium. Measurements were performed in 24 patients receiving MV immediately before and at the end of a 30-min SBT. Blood flow index (BFI), DO2, and %StiO2 in the prefrontal cortex, scalene, rectus abdominis, and thenar muscle were simultaneously assessed by near-infrared spectroscopy using the tracer indocyanine green dye. Cardiac output, arterial blood gases, and systemic oxygenation were also recorded. RESULTS: During the SBT, prefrontal cortex BFI and DO2 responses did not differ between SBT-failure and SBT-success groups (p > 0.05). However, prefrontal cortex %StiO2 decreased in six of eight patients (75%) in the SBT-failure group (median [interquartile range 25-75%]: MV = 57.2% [49.1-61.7] vs. SBT = 51.0% [41.5-62.5]) compared to 3 of 16 patients (19%) in the SBT-success group (median [interquartile range 25-75%]: MV = 65.0% [58.6-68.5] vs. SBT = 65.1% [59.5-71.1]), resulting in a significant differential %StiO2 response between groups (p = 0.031). Similarly, a significant differential response in thenar muscle %StiO2 (p = 0.018) was observed between groups. A receiver operating characteristic analysis identified a decrease in prefrontal cortex %StiO2 > 1.6% during the SBT as an optimal cutoff, with a sensitivity of 94% and a specificity of 75% to predict SBT failure and an area under the curve of 0.79 (95% CI: 0.55-1.00). Cardiac output, systemic oxygenation, scalene, and rectus abdominis BFI, DO2, and %StiO2 responses did not differ between groups (p > 0.05); however, during the SBT, a significant positive association in prefrontal cortex BFI and partial pressure of arterial carbon dioxide was observed only in the SBT-success group (SBT success: Spearman's ρ = 0.728, p = 0.002 vs. SBT failure: ρ = 0.048, p = 0.934). CONCLUSIONS: This study demonstrated a reduced differential response in prefrontal cortex %StiO2 in the SBT-failure group compared with the SBT-success group possibly due to the insufficient increase in prefrontal cortex perfusion in SBT-failure patients. A > 1.6% drop in prefrontal cortex %StiO2 during SBT was sensitive in predicting SBT failure. Further research is needed to validate these findings in a larger population and to evaluate whether cerebral cortex %StiO2 measurements by near-infrared spectroscopy can assist in the decision-making process on liberation from MV.

Near-infrared spectroscopy measures of sternocleidomastoid blood flow during exercise and hyperpnoea.

NEW FINDINGS: What is the central question of this study? How does sternocleidomastoid blood flow change in response to increasing ventilation and whole-body exercise intensity? What is the main finding and its importance? Sternocleidomastoid blood flow increased with increasing ventilation. For a given ventilation, sternocleidomastoid blood flow was lower during whole-body exercise compared to resting hyperpnoea. These findings suggest that locomotor muscle work exerts an effect on respiratory muscle blood flow that can be observed in the sternocleidomastoid. ABSTRACT: Respiratory muscle work influences the distribution of blood flow during exercise. Most studies have focused on blood flow to the locomotor musculature rather than the respiratory muscles, owing to the complex anatomical arrangement of respiratory muscles. The purpose of this study was to examine how accessory respiratory (i.e. sternocleidomastoid, and muscles in the intercostal space) muscle blood flow changes in response to locomotor muscle work. Seven men performed 5 min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5 min bouts of voluntary hyperpnoea (VH) matching the ventilation achieved during each exercise (EX) trial. Blood-flow index (BFI) of the vastus lateralis, sternocleidomastoid (SCM) and seventh intercostal space (IC) were estimated using near-infrared spectroscopy and indocyanine green and expressed relative to resting levels. BFISCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFISCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFIIC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFIIC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFIIC between conditions (P > 0.05). BFISCM was lower for a given minute ventilation during EX compared to VH, suggesting that accessory respiratory muscle blood flow is influenced by whole-body exercise.

Plateau Waves of Intracranial Pressure and Multimodal Brain Monitoring.

The aim of this study was to describe multimodal brain monitoring characteristics during plateau waves of intracranial pressure (ICP) in patients with head injury, using ICM+ software for continuous recording. Plateau waves consist of an abrupt elevation of ICP above 40 mmHg for 5-20 min. This is a prospective observational study of patients with head injury who were admitted to a neurocritical care unit and who developed plateau waves. We analyzed 59 plateau waves that occurred in 8 of 18 patients (44 %). At the top of plateau waves arterial blood pressure remained almost constant, but cerebral perfusion pressure, cerebral blood flow, brain tissue oxygenation, and cerebral oximetry decreased. After plateau waves, patients with a previously better autoregulation status developed hyperemia, demonstrated by an increase in cerebral blood flow and brain oxygenation. Pressure and oxygen cerebrovascular reactivity indexes (pressure reactivity index and ORxshort) increased significantly during the plateau wave as a sign of disruption of autoregulation. Bedside multimodal brain monitoring is important to characterize increases in ICP and give differential diagnoses of plateau waves, as management of this phenomenon differs from that of regular ICP.

Interleaved imaging of cerebral hemodynamics and blood flow index to monitor ischemic stroke and treatment in rat by volumetric diffuse optical tomography.

Diffuse optical tomography (DOT) has been used by several groups to assess cerebral hemodynamics of cerebral ischemia in humans and animals. In this study, we combined DOT with an indocyanine green (ICG)-tracking method to achieve interleaved images of cerebral hemodynamics and blood flow index (BFI) using two middle cerebral artery occlusion (MCAO) rat models. To achieve volumetric images with high-spatial resolution, we first integrated a depth compensation algorithm (DCA) with a volumetric mesh-based rat head model to generate three-dimensional (3D) DOT on a rat brain atlas. Then, the experimental DOT data from two rat models were collected using interleaved strategy for cerebral hemodynamics and BFI during and after ischemic stroke, with and without a thrombolytic therapy for the embolic MCAO model. The acquired animal data were further analyzed using the integrated rat-atlas-guided DOT method to form time-evolving 3D images of both cerebral hemodynamics and BFI. In particular, we were able to show and identify therapeutic outcomes of a thrombolytic treatment applied to the embolism-induced ischemic model. This paper demonstrates that volumetric DOT is capable of providing high-quality, interleaved images of cerebral hemodynamics and blood perfusion in small animals during and after ischemic stroke, with excellent 3D visualization and quantifications.

DCS blood flow index underestimates skeletal muscle perfusion in vivo: rationale and early evidence for the NIRS-DCS perfusion index.

Significance: Diffuse correlation spectroscopy (DCS) permits non-invasive assessment of skeletal muscle blood flow but may misestimate changes in muscle perfusion. Aim: We aimed to highlight recent evidence that DCS blood flow index (BFI) misestimates changes in muscle blood flow during physiological perturbation and to introduce a novel approach that adjusts BFI for estimated changes in vasodilation. Approach: We measured changes in muscle BFI during quadriceps and forearm exercises using DCS, the latter of which were adjusted for estimated changes in microvascular flow area and then compared to Doppler ultrasound in the brachial artery. Then, we compared adjusted BFI- and arterial spin labeling (ASL) MRI measures of gastrocnemius blood flow during reactive hyperemia and plantar flexion exercise. Results: We observed little-to-no change in quadriceps BFI during maximal-effort exercise. Similarly, forearm BFI was modestly increased during handgrip exercise, but the magnitude was significantly lower than measured by Doppler ultrasound in the brachial artery. However, this difference was ameliorated after adjusting BFI for estimated changes in microvascular flow area. Similar observations were also observed in the gastrocnemius when directly comparing the adjusted BFI values to ASL-MRI. Conclusions: Adjusting BFI for estimated changes in microvascular flow area may improve DCS estimates of muscle blood flow, but further study is needed to validate these methods moving forward.

Interferometric diffuse optics: recent advances and future outlook.

The field of diffuse optics has provided a rich set of neurophotonic tools to measure the human brain noninvasively. Interferometric detection is a recent, exciting methodological development in this field. The approach is especially promising for the measurement of diffuse fluctuation signals related to blood flow. Benefitting from inexpensive sensor arrays, the interferometric approach has already dramatically improved throughput, enabling the measurement of brain blood flow faster and deeper. The interferometric approach can also achieve time-of-flight resolution, improving the accuracy of acquired signals. We provide a historical perspective and summary of recent work in the nascent area of interferometric diffuse optics. We predict that the convergence of interferometric technology with existing economies of scale will propel many advances in the years to come.

Assessing the Sensitivity of Multi-Distance Hyperspectral NIRS to Changes in the Oxidation State of Cytochrome C Oxidase in the Brain.

Near-infrared spectroscopy (NIRS) measurements of tissue oxygen saturation (StO2) are frequently used during vascular and cardiac surgeries as a non-invasive means of assessing brain health; however, signal contamination from extracerebral tissues remains a concern. As an alternative, hyperspectral (hs)NIRS can be used to measure changes in the oxidation state of cytochrome c oxidase (ΔoxCCO), which provides greater sensitivity to the brain given its higher mitochondrial concentration versus the scalp. The purpose of this study was to evaluate the depth sensitivity of the oxCCO signal to changes occurring in the brain and extracerebral tissue components. The oxCCO assessment was conducted using multi-distance hsNIRS (source-detector separations = 1 and 3 cm), and metabolic changes were compared to changes in StO2. Ten participants were monitored using an in-house system combining hsNIRS and diffuse correlation spectroscopy (DCS). Data were acquired during carotid compression (CC) to reduce blood flow and hypercapnia to increase flow. Reducing blood flow by CC resulted in a significant decrease in oxCCO measured at rSD = 3 cm but not at 1 cm. In contrast, significant changes in StO2 were found at both distances. Hypercapnia caused significant increases in StO2 and oxCCO at rSD = 3 cm, but not at 1 cm. Extracerebral contamination resulted in elevated StO2 but not oxCCO after hypercapnia, which was significantly reduced by applying regression analysis. This study demonstrated that oxCCO was less sensitive to extracerebral signals than StO2.

The role of diffuse correlation spectroscopy and frequency-domain near-infrared spectroscopy in monitoring cerebral hemodynamics during hypothermic circulatory arrests.

OBJECTIVES: Real-time noninvasive monitoring of cerebral blood flow (CBF) during surgery is key to reducing mortality rates associated with adult cardiac surgeries requiring hypothermic circulatory arrest (HCA). We explored a method to monitor cerebral blood flow during different brain protection techniques using diffuse correlation spectroscopy (DCS), a noninvasive optical technique which, combined with frequency-domain near-infrared spectroscopy (FDNIRS), also provides a measure of oxygen metabolism. METHODS: We used DCS in combination with FDNIRS to simultaneously measure hemoglobin oxygen saturation (SO2), an index of cerebral blood flow (CBFi), and an index of cerebral metabolic rate of oxygen (CMRO2i) in 12 patients undergoing cardiac surgery with HCA. RESULTS: Our measurements revealed that a negligible amount of blood is delivered to the cerebral cortex during HCA with retrograde cerebral perfusion, indistinguishable from HCA-only cases (median CBFi drops of 93% and 95%, respectively) with consequent similar decreases in SO2 (mean decrease of 0.6 ± 0.1% and 0.9 ± 0.2% per minute, respectively); CBFi and SO2 are mostly maintained with antegrade cerebral perfusion; the relationship of CMRO2i to temperature is given by CMRO2i = 0.052e0.079T. CONCLUSIONS: FDNIRS-DCS is able to detect changes in CBFi, SO2, and CMRO2i with intervention and can become a valuable tool for optimizing cerebral protection during HCA.

Correlation of color Doppler ultrasound and pathological grading in endometrial carcinoma.

INTRODUCTION: Given the role of angiogenesis in tumor growth, the evaluation of tissue vascularization by Doppler ultrasound has been thought to be useful in the prediction of malignant endometrial changes. The aim of this study was to evaluate the efficacy of transvaginal color Doppler ultrasound (TV-CDU) findings in the differentiation between endometrial hyperplasia and endometrial carcinoma and its relation with pathologic findings. METHODS: This observational study included 48 women with either endometrial hyperplasia (n = 10) or endometrial carcinoma (n = 38) that had been diagnosed by endometrial biopsy. The intratumoral blood flow characteristics including resistance (RI), pulsatility (PI) and peak systolic velocity (PSV) index were analyzed using TV-CDU before surgery. Endometrial thickness and myometrial invasion also was assessed in all patients using gray-scale ultrasound. Then the relationship between these ultrasound findings and histologic results was evaluated with EC. RESULTS: RI, PI, and PSV indices in endometrial carcinoma were significantly higher than endometrial hyperplasia (P < 0.0001). There was also a significant difference between the mean endometrial thickness between the two groups of endometrial hyperplasia and endometrial carcinoma (P < 0.0001). Intratumoral blood flow index were higher in high grade tumors than in low grade tumors (P < 0.05). CONCLUSION: TV-CDU may be useful to show a difference the difference in tumor angiogenesis between endometrial hyperplasia and endometrial carcinoma and therefore be used in differentiation of endometrial hyperplasia and carcinoma. Evaluation of intratumoral blood flow using RI, PI, and PSV indices in patients with endometrial carcinoma may be helpful distinguishing between low-grade and high-grade tumors as well as preoperative tumor invasion before surgery.

Variation of Cognitive Function During a Short Stay at Hypobaric Hypoxia Chamber (Altitude: 3842 M).

OBJECTIVE: To observe the effects of a fast-acute ascent to high altitude on brain cognitive function and transcranial doppler parameters in order to understand the physiological countermeasures of hypoxia. METHODS: 17 high-altitude-naïve male subjects (mean age was 26.3 ± 8.1 years) participated in the study. We measured Critical Flicker Fusion Frequency (CFFF), blood oxygen saturation, Psychology Experiment Building (PEBL) including three tests (Modified Math Processing Task, Perceptual Vigilance Task, and Time Estimation Task), as well as Cerebral Blood Flow index (CBFi), mean cerebral artery Systolic and diastolic velocities, Cerebral Pulsatility index (CPi), and heart Rate. All were measured at sea level, at least 1 h after arrival at the hypobaric hypoxia equivalent of 3842 m and 1 h after return to sea level. RESULTS: Under acute exposure to hypobaric hypoxic conditions, significant decrease in CFFF [42.1 ± 1 vs. 43.5 ± 1.7 Hz at sea level (asl), p < 0.01], CBFi (611 ± 51 vs. 665 ± 71 asl, p < 0.01) and blood oxygen saturation (83 ± 4% vs. 98 ± 1% asl, p < 0.001) as compared to pre-ascent values were observed. Physiological countermeasures to hypoxia could be involved as there was no significant change in neuropsychometric tests, Systolic and Diastolic velocities and CPi. A significant increase in Heart Rate (81 ± 15 bpm vs. 66 ± 15 bpm asl, p < 0.001) was observed. All parameters returned to their basal values 1 h after regaining sea level. CONCLUSION: Hypoxia results in a decrease in CFFF, CBFi and oxygen saturation and in an increase in heart rate. As it decreased, Cerebral Blood Flow index does not seem to be the physiological measurement of choice to hypoxia explaining the maintenance of cognitive performance after acute exposure to hypobaric hypoxia and requires further investigation. Cerebral oxygen delivery and extraction could be one of the underlying mechanisms.

Assessment of skin blood flow following spinal manual therapy: a systematic review.

Skin blood flow (SBF) indexes have been used to describe physiological mechanisms associated with spinal manual therapy (SMT). The aims of the current review were to assess methods for data collection, assess how investigators interpreted SBF changes, and formulate recommendations to advance manual medicine research. A database search was performed in PubMed, Cochrane Library, the Physiotherapy Evidence Database, and the Cumulative Index to Nursing and Allied Health Literature through April 2014. Articles were included if at least 1 outcome measure was changes in 1 SBF index following SMT. The database search yielded 344 records. Two independent authors applied the inclusion criteria. Twenty studies met the inclusion criteria. Selected studies used heterogeneous methods to assess short-term post-SMT changes in SBF, usually vasoconstriction, which was interpreted as a general sympathoexcitatory effect through central mechanisms. However, this conclusion might be challenged by the current understanding of skin sympathetic nervous activity over local endothelial mechanisms that are specifically controlling SBF. Evaluation of SBF measurements in peripheral tissues following SMT may document physiological responses that are beyond peripheral sympathetic function. Based on the current use of SBF indexes in clinical and physiological research, 14 recommendations for advancing manual medicine research using laser Doppler flowmetry are presented.