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Sleep Disordered Breathing (SDB) is a common disease associated with increased risk for cardiometabolic, cardiovascular, and cognitive diseases. How SDB affects the molecular environment is still poorly understood. We study the association of three SDB measures with gene expression measured using RNA-seq in multiple blood tissues from the Multi-Ethnic Study of Atherosclerosis. We develop genetic instrumental variables for the associated transcripts as polygenic risk scores (tPRS), then generalize and validate the tPRS in the Women's Health Initiative. We measure the associations of the validated tPRS with SDB and serum metabolites in Hispanic Community Health Study/Study of Latinos. Here we find differential gene expression by blood cell type in relation to SDB traits and link P2XR4 expression to average oxyhemoglobin saturation during sleep and butyrylcarnitine (C4) levels. These findings can be used to develop interventions to alleviate the effect of SDB on the human molecular environment.

Study objectivesChronic mountain sickness (CMS) is commonly observed among Andean and other highland populations. Sleep-disordered breathing (SDB) is highly prevalent at high altitude, and SDB and nocturnal hypoxemia have been observed in CMS. Phlebotomy is commonly performed to treat CMS, but it is unknown whether reducing hematocrit improves SDB. We hypothesized that isovolemic hemodilution (IVHD) in CMS would reduce SBD severity and improve sleep efficiency.MethodsSix participants with CMS and 8 without CMS, all residents of Cerro de Pasco, Peru (altitude 4340 m), completed baseline nocturnal sleep studies. CMS participants then underwent IVHD, and nocturnal sleep studies were repeated 24-48 hours after IVHD. We analyzed sleep apnea severity, nocturnal oxygenation, and sleep quality in those with CMS relative to those without CMS, and the effects of IVHD in CMS participants.ResultsParticipants with CMS did not have altered sleep architecture, sleep apnea severity, or nocturnal oxygenation relative to non-CMS participants. However, IVHD in CMS increased apnea-hypopnea index (40.9 ± 6.9 events/h to 61.5 ± 7.7 events/h, P = .009). IVHD increased oxyhemoglobin desaturation index (P = .008) and the percentage of sleep time spent with oxyhemoglobin saturation at or below 80% (P = .012). There was no effect of IVHD on sleep efficiency, arousal index, or sleep staging.ConclusionsIn this cohort, CMS was not associated with worsened SDB or changes in sleep architecture. IVHD, a putative therapeutic option for participants with CMS, appears to worsen nocturnal oxygenation and SDB within 48 hours post-IVHD.CitationSanchez-Azofra A, Villafuerte FC, DeYoung PN, et al. Isovolemic hemodilution in chronic mountain sickness acutely worsens nocturnal oxygenation and sleep apnea severity. J Clin Sleep Med. 2022;18(10):2423-2432.

BACKGROUND: The local hemodynamic response after cupping therapy has been considered as a contributing factor for improving muscle tissue health; however, the effects of cupping pressure and duration on the spatial hemodynamic response have not been investigated. OBJECTIVE: The objective of this study was to investigate the hemodynamic response inside and outside the cupping cup under various pressures and durations of cupping therapy. METHODS: A 3-way factorial design with repeated measures was used to investigate the main and interaction effects of the location (areas inside and outside the cup), pressure (- 225 and - 300 mmHg) and duration (5 and 10 min) on the hemodynamic response of the biceps muscle. A functional near-infrared spectroscopy was used to assess hemodynamic changes in 18 participants. RESULTS: A significant three-way interaction of the location, pressure, and duration factors was observed in oxyhemoglobin (p = 0.023), deoxy-hemoglobin (p = 0.013), and blood volume (p = 0.013). A significant increase was observed in oxyhemoglobin, blood volume, and oxygenation compared to pre-cupping (p < 0.05) in the area outside the cup. CONCLUSION: Our findings indicate that an appropriate combination of cupping pressure and duration can effectively affect the spatial hemodynamic response of the biceps. [ABSTRACT FROM AUTHOR]

White seabass (Atractoscion nobilis) increasingly experience periods of low oxygen (O2; hypoxia) and high carbon dioxide (CO2, hypercapnia) due to climate change and eutrophication of the coastal waters of California. Hemoglobin (Hb) is the principal O2 carrier in the blood and in many teleost fishes Hb-O2 binding is compromised at low pH; however, the red blood cells (RBC) of some species regulate intracellular pH with adrenergically stimulated sodium-proton-exchangers (β-NHEs). We hypothesized that RBC β-NHEs in white seabass are an important mechanism that can protect the blood O2-carrying capacity during hypoxia and hypercapnia. We determined the O2-binding characteristics of white seabass blood, the cellular and subcellular response of RBCs to adrenergic stimulation, and quantified the protective effect of β-NHE activity on Hb-O2 saturation. White seabass had typical teleost Hb characteristics, with a moderate O2 affinity (Po2 at half-saturation; P50 2.9 kPa) that was highly pH-sensitive (Bohr coefficient -0.92; Root effect 52%). Novel findings from super-resolution microscopy revealed β-NHE protein in vesicle-like structures and its translocation into the membrane after adrenergic stimulation. Microscopy data were corroborated by molecular and phylogenetic results and a functional characterization of β-NHE activity. The activation of RBC β-NHEs increased Hb-O2 saturation by ∼8% in normoxic hypercapnia and by up to ∼20% in hypoxic normocapnia. Our results provide novel insight into the cellular mechanism of adrenergic RBC stimulation within an ecologically relevant context. β-NHE activity in white seabass has great potential to protect arterial O2 transport during hypoxia and hypercapnia but is less effective during combinations of these stressors.

Background: Decreased systemic oxygen delivery derived from gas exchange abnormalities in severe hemolysis complicates patients requiring mechanical circulatory support devices. Severe hemolysis releases free hemoglobin in plasma causing elevation of carboxyhemoglobin and methemoglobin levels. Hemolysis-induced decline in hemoglobin and oxyhemoglobin saturation significantly reduces the arterial oxygen content in blood, reducing systemic oxygen delivery. These patients develop hypoxemia with misleadingly normal oxygen saturation measured by standard pulse oximetry. Methods: Retrospective review of 2 clinical cases reaching carboxyhemoglobin and methemoglobin levels > 2% while supported with an Impella device. Results: Case 1. Patient with cardiogenic shock refractory to maximal medical therapy required insertion of Impella device achieving improvement in cardiac output, pulse oximetry, arterial oxygen saturation and systemic oxygen delivery. The device caused significant hemolytic anemia with severe decline in hemoglobin and arterial oxygen saturation with elevation of carboxyhemoglobin and methemoglobin levels, causing drastic reduction in systemic oxygen delivery despite adequate cardiac output. Device removal reversed severe hemolytic anemia, causing increased arterial oxygen saturation and systemic oxygen delivery despite borderline cardiac output.Case 2. Patient with refractory cardiogenic shock improved after insertion of Impella device. Initial improvement cardiac output and systemic oxygen delivery was negated by hemolytic anemia associated with elevation of carboxyhemoglobin and methemoglobin levels. Hemolysis decreased by reducing the Impella power output. Carboxyhemoglobin and methemoglobin levels correlated precisely with degree of hemolysis allowing to titrate therapy to best systemic oxygen delivery. Conclusions: Monitoring carboxyhemoglobin and methemoglobin levels readily identifies patients with ongoing hemolysis secondary to invasive supportive devices.

BackgroundPerioperative pulse oximetry hemoglobin saturation (Spo2) measurement is associated with fewer desaturation and hypoxia episodes. However, the sigmoidal nature of oxygen-hemoglobin dissociation limits the accuracy of estimation of the partial pressure of oxygen (Pao2) >80 mm Hg and correspondingly limits the ability to identify when Pao2 >80 mm Hg but falling. We hypothesized that a proxy measurement for oxygen saturation (Oxygen Reserve Index [ORI]) derived from multiwavelength pulse oximetry may allow additional warning time before critical desaturation or hypoxia. To test our hypothesis, we used a Masimo multiwavelength pulse oximeter to compare ORI and Spo2 warning times during apnea in high-risk surgical patients undergoing cardiac surgery.MethodsThis institutional review board-approved prospective study (NCT03021473) enrolled American Society of Anesthesiologists physical status III or IV patients scheduled for elective surgery with planned preinduction arterial catheter placement. In addition to standard monitors, an ORI sensor was placed and patients were monitored with a pulse oximeter displaying the ORI, a nondimensional parameter that ranges from 0 to 1. Patients were then preoxygenated until ORI plateaued. Following induction of anesthesia, mask ventilation with 100% oxygen was performed until neuromuscular blockade was established. Endotracheal intubation was accomplished using videolaryngoscopy to confirm placement. The endotracheal tube was not connected to the breathing circuit, and patients were allowed to be apneic. Ventilation was resumed when Spo2 reached 94%. We defined ORI warning time as the time from when the ORI alarm registered (based on the absolute value and the rate of change) until the Spo2 decreased to 94%. We defined the Spo2 warning time as the time for Spo2 to decrease from 97% to 94%. The added warning time provided by ORI was defined as the difference between ORI warning time and Spo2 warning time.ResultsForty subjects were enrolled. Complete data for analysis were available from 37 patients. The ORI alarm registered before Spo2 decreasing to 97% in all patients. Median (interquartile range [IQR]) ORI warning time was 80.4 seconds (59.7-105.9 seconds). Median (IQR) Spo2 warning time was 29.0 seconds (20.5-41.0 seconds). The added warning time provided by ORI was 48.4 seconds (95% confidence interval [CI], 40.4-62.0 seconds; P < .0001).ConclusionsIn adult high-risk surgical patients, ORI provided clinically relevant added warning time of impending desaturation compared to Spo2. This additional time may allow modification of airway management, earlier calls for help, or assistance from other providers. The potential patient safety impact of such monitoring requires further study.

BackgroundSleep Disordered Breathing (SDB) is associated with a wide range of pathophysiological changes due, in part, to hypoxemia during sleep. We sought to identify gene transcription associations with measures of SDB and hypoxemia during sleep, and study their response to treatment.MethodsIn two discovery cohorts, Framingham Offspring Study (FOS; N = 571) and the Multi-Ethnic Study of Atherosclerosis (MESA; N = 580), we studied gene expression in peripheral blood mononuclear cells in association with three measures of SDB: Apnea Hypopnea Index (AHI); average oxyhemoglobin saturation (avgO2) during sleep; and minimum oxyhemoglobin saturation (minO2) during sleep. Associated genes were used for analysis of gene expression in the blood of 15 participants with moderate or severe obstructive sleep apnea (OSA) from the Heart Biomarkers In Apnea Treatment (HeartBEAT) trial. These genes were studied pre- and post-treatment (three months) with continuous positive airway pressure (CPAP). We also performed Gene Set Enrichment Analysis (GSEA) on all traits and cohort analyses.FindingsTwenty-two genes were associated with SDB traits in both MESA and FOS. Of these, lower expression of CD1D and RAB20 was associated with lower avgO2 in MESA and FOS. CPAP treatment increased the expression of these genes in HeartBEAT participants. Immunity and inflammation pathways were up-regulated in subjects with lower avgO2; i.e., in those with a more severe SDB phenotype (MESA), whereas immuno-inflammatory processes were down-regulated following CPAP treatment (HeartBEAT).InterpretationLow oxygen saturation during sleep is associated with alterations in gene expression and transcriptional programs that are partially reversed by CPAP treatment.

Significance: Spatial frequency domain imaging (SFDI) is a diffuse optical measurement technique that can quantify tissue optical absorption (μa) and reduced scattering (μs') on a pixel-by-pixel basis. Measurements of μa at different wavelengths enable the extraction of molar concentrations of tissue chromophores over a wide field, providing a noncontact and label-free means to assess tissue viability, oxygenation, microarchitecture, and molecular content. We present here openSFDI: an open-source guide for building a low-cost, small-footprint, three-wavelength SFDI system capable of quantifying μa and μs' as well as oxyhemoglobin and deoxyhemoglobin concentrations in biological tissue. The companion website provides a complete parts list along with detailed instructions for assembling the openSFDI system. Aim: We describe the design of openSFDI and report on the accuracy and precision of optical property extractions for three different systems fabricated according to the instructions on the openSFDI website. Approach: Accuracy was assessed by measuring nine tissue-simulating optical phantoms with a physiologically relevant range of μa and μs' with the openSFDI systems and a commercial SFDI device. Precision was assessed by repeatedly measuring the same phantom over 1 h. Results: The openSFDI systems had an error of 0  ±  6  %   in μa and -2  ±  3  %   in μs', compared to a commercial SFDI system. Bland-Altman analysis revealed the limits of agreement between the two systems to be   ±  0.004  mm  -  1 for μa and -0.06 to 0.1  mm  -  1 for μs'. The openSFDI system had low drift with an average standard deviation of 0.0007  mm  -  1 and 0.05  mm  -  1 in μa and μs', respectively., Conclusion: The openSFDI provides a customizable hardware platform for research groups seeking to utilize SFDI for quantitative diffuse optical imaging.

Objective To investigate the changes of brain activation and brain network connectivity in patients with spinal cord injury (SCI). Methods A total of 20 patients with SCI were selected from Qilu Hospital of Shandong University from January to October 2021, including 8 patients with simple lower extremity involvement (paraplegia group) and 12 patients with all limbs involvement (tetraplegia group), and 10 healthy controls with matched baseline data with the SCI group were included in the same period. Functional near⁃infrared spectroscopy (fNIRS) was used to collect the data of cerebral oxyhemoglobin (HbO2) in the bilateral prefrontal lobe (LPFC/RPFC), motor cortex (LMC/RMC) and occipital lobe (LOL/ROL). The resting HbO2 β values was calculated by generalized linear model to evaluate the activation degree of the cerebral cortex covered by different detection channels, the correlation between HbO2 β values was calculated by Pearson correlation analysis and partial correlation to analysis different detection channels [partial correlation coefficient (r) was defined as functional connectivity strength] to evaluate the functional connectivity of the brain network. Results 1) Degree of brain activation: compared with the control group, the HbO2 β values corresponding to channel 2 (t=⁃2.482, P=0.020), channel 8 (t=⁃3.315, P=0.003) and channel 16 (t=⁃2.738, P=0.011) was increased in the tetraplegia group, while the HbO2 β value corresponding to channel 25 was decreased (t=2.104, P=0.045), and the HbO2 β value of channel 8 was increased (t=⁃2.475, P=0.020) in paraplegia group. Compared with the tetraplegia group, the HbO2 β values in channel 17 (t=2.552, P=0.017) and channel 25 (t=2.342, P=0.027) were increased in the paraplegia group. The value of HbO2 β in the left prefrontal lobe of tetraplegia group was significantly higher than that of control group (t=2.652, P=0.013). 2) The number of functional connections between different channels and cerebral cortex: the proportion of channels related to motor cortex in different groups was 94.12% in the paraplegia group (32/34), 82.76% in the tetraplegia group (24/29), and only 74.36% in the control group (29/39). 3) Functional connectivity strength in the brain: compared with the control group, the functional connectivity strength in the right motor area was weakened in both the paraplegia group (t=4.572, P=0.000) and the tetraplegia group (t=4.822, P=0.000). Conclusions There are abnormalities in resting brain activation and functional connectivity of brain network after SCI, which are manifested as local enhancement of spontaneous neural activity in some brain regions and abnormal functional connectivity in cerebral cortices and brain regions.

Quantitative diffuse optical imaging has the potential to provide valuable functional information about tissue status, such as oxygen saturation or blood content to healthcare practitioners in real time. However, significant technical challenges have so far prevented such tools from being deployed in the clinic. Toward achieving this goal, prior research introduced methods based on spatial frequency domain imaging (SFDI) that allow real-time (within milliseconds) wide-field imaging of optical properties but at a single wavelength. However, for this technology to be useful to clinicians, images must be displayed in terms of metrics related to the physiological state of the tissue, hence interpretable to guide decision-making. For this purpose, recent developments introduced multispectral SFDI methods for rapid imaging of oxygenation parameters up to 16 frames per seconds (fps). We introduce real-time, wide-field, and quantitative blood parameters imaging using spatiotemporal modulation of light. Using this method, we are able to quantitatively obtain optical properties at 100 fps at two wavelengths (665 and 860 nm), and therefore oxygenation, oxyhemoglobin, and deoxyhemoglobin, using a single camera with, at most, 4.2% error in comparison with standard SFDI acquisitions.

Burn wounds and wound healing invoke several biological processes that may complicate the interpretation of spectral imaging data. Through analysis of spatial frequency domain spectroscopy data (450 to 1000 nm) obtained from longitudinal investigations using a graded porcine burn wound healing model, we have identified features in the absorption spectrum that appear to suggest the presence of hemoglobin breakdown products, e.g., methemoglobin. Our results show that the calculated concentrations of methemoglobin directly correlate with burn severity, 24 h after the injury. In addition, tissue parameters such as oxygenation (StO2) and water fraction may be underestimated by 20% and 78%, respectively, if methemoglobin is not included in the spectral analysis.

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.

Transmission-mode pulse oximetry, the optical method for determining oxygen saturation in blood, is limited to only tissues that can be transilluminated, such as the earlobes and the fingers. The existing sensor configuration provides only single-point measurements, lacking 2D oxygenation mapping capability. Here, we demonstrate a flexible and printed sensor array composed of organic light-emitting diodes and organic photodiodes, which senses reflected light from tissue to determine the oxygen saturation. We use the reflectance oximeter array beyond the conventional sensing locations. The sensor is implemented to measure oxygen saturation on the forehead with 1.1% mean error and to create 2D oxygenation maps of adult forearms under pressure-cuff-induced ischemia. In addition, we present mathematical models to determine oxygenation in the presence and absence of a pulsatile arterial blood signal. The mechanical flexibility, 2D oxygenation mapping capability, and the ability to place the sensor in various locations make the reflectance oximeter array promising for medical sensing applications such as monitoring of real-time chronic medical conditions as well as postsurgery recovery management of tissues, organs, and wounds.

Conflicting evidence has suggested that low mean nocturnal hemoglobin oxygen saturation (SpO2 ) predicts future hospital days for acute severe pain in children with sickle cell anemia (SCA). In an unselected multicenter prospective cohort study, we tested the hypothesis that either low mean nocturnal SpO2 or high obstructive apnea-hypopnea index (OAHI; the number of obstructive apneas and hypopneas with ≥ 3% desaturation or arousal per hour of sleep) or high oxygen desaturation index (ODI; number of ≥ 3% desaturation from baseline saturation per hour of sleep) is associated with increased incidence rates of pain. A total of 140 children with SCA with a median age of 10.8 years (interquartile range 7.2) were followed for a median of 4.9 years (interquartile range 1.8). Overnight polysomnography evaluations at baseline health exam were measured and adjudicated centrally. Multivariable models created in two steps were included. First, all plausible covariates were included in a screening model. Subsequently, covariates meeting level of statistical significance of P

The tissue metabolic rate of oxygen consumption (tMRO2) is a clinically relevant marker for a number of pathologies including cancer and arterial occlusive disease. We present and validate a noncontact method for quantitatively mapping tMRO2 over a wide, scalable field of view at 16  frames  /  s. We achieve this by developing a dual-wavelength, near-infrared coherent spatial frequency-domain imaging (cSFDI) system to calculate tissue optical properties (i.e., absorption, μa, and reduced scattering, μs', parameters) as well as the speckle flow index (SFI) at every pixel. Images of tissue oxy- and deoxyhemoglobin concentration (  [  HbO2  ]   and [HHb]) are calculated from optical properties and combined with SFI to calculate tMRO2. We validate the system using a series of yeast-hemoglobin tissue-simulating phantoms and conduct in vivo tests in humans using arterial occlusions that demonstrate sensitivity to tissue metabolic oxygen debt and its repayment. Finally, we image the impact of cyanide exposure and toxicity reversal in an in vivo rabbit model showing clear instances of mitochondrial uncoupling and significantly diminished tMRO2. We conclude that dual-wavelength cSFDI provides rapid, quantitative, wide-field mapping of tMRO2 that can reveal unique spatial and temporal dynamics relevant to tissue pathology and viability.

ObjectiveTo quantitatively measure tissue composition and hemodynamics during resuscitative endovascular balloon occlusion of the aorta (REBOA) in two tissue compartments using non-invasive two-channel broadband diffuse optical spectroscopy (DOS).MethodsTissue concentrations of oxy- and deoxyhemoglobin (HbO2 and HbR), water, and lipid were measured in a porcine model (n = 10) of massive hemorrhage (65% total blood volume over 1 h) and 30-min REBOA superior and inferior to the aortic balloon.ResultsAfter hemorrhage, hemoglobin oxygen saturation (StO2 = HbO2/[HbO2 + HbR]) at both sites decreased significantly (-29.9% and -42.3%, respectively). The DOS measurements correlated with mean arterial pressure (MAP) (R2 = 0.79, R2 = 0.88), stroke volume (SV) (R2 = 0.68, R2 = 0.88), and heart rate (HR) (R2 = 0.72, R2 = 0.88). During REBOA, inferior StO2 continued to decline while superior StO2 peaked 12 min after REBOA before decreasing again. Inferior DOS parameters did not associate with MAP, SV, or HR during REBOA.ConclusionsDual-channel regional tissue DOS measurements can be used to non-invasively track the formation of hemodynamically distinct tissue compartments during hemorrhage and REBOA. Conventional systemic measures MAP, HR, and SV are uncorrelated with tissue status in inferior (downstream) sites. Multi-compartment DOS may provide a more complete picture of the efficacy of REBOA and similar resuscitation procedures.

Objective To investigate the changes of brain activation and brain network connectivity in patients with spinal cord injury (SCI). Methods A total of 20 patients with SCI were selected from Qilu Hospital of Shandong University from January to October 2021, including 8 patients with simple lower extremity involvement (paraplegia group) and 12 patients with all limbs involvement (tetraplegia group), and 10 healthy controls with matched baseline data with the SCI group were included in the same period. Functional near-infrared spectroscopy (fNIRS) was used to collect the data of cerebral oxyhemoglobin (HbO7) in the bilateral prefrontal lobe (LPFC/RPFC), motor cortex (LMC/RMC) and occipital lobe (LOL/ROL). The resting HM^ P values was calculated by generalized linear model to evaluate the activation degree of the cerebral cortex covered by different detection channels, the correlation between HbO7 P values was calculated by Pearson correlation analysis and partial correlation to analysis different detection channels [partial correlation coefficient (r) was defined as functional connectivity strength] to evaluate the functional connectivity of the brain network. Results 1) Degree of brain activation: compared with the control group, the HbO2 (3 values corresponding to channel 2 (t = -2.482, P = 0.020), channel 8 (t = -3.315, P =0.003) and channel 16 (t = - 2.738, P = 0.011) was increased in the tetraplegia group, while the HbO, (3 value corresponding to channel 25 was decreased (t = 2.104, P = 0.045), and the HbO, (3 value of channel 8 was increased (t = - 2.475, P = 0.020) in paraplegia group. Compared with the tetraplegia group, the HbO7 (3 values in channel 17 (t = 2.552, P = 0.017) and channel 25 (t = 2.342, P = 0.027) were increased in the paraplegia group. The value of HbO7 (3 in the left prefrontal lobe of tetraplegia group was significantly higher than that of control group (t = 2.652, P = 0.013). 2) The number of functional connections between different channels and cerebral cortex: the proportion of channels related to motor cortex in different groups was 94.12% in the paraplegia group (32/34), 82.76% in the tetraplegia group (24/29), and only 74.36% in the control group (29/39). 3) Functional connectivity strength in the brain: compared with the control group, the functional connectivity strength in the right motor area was weakened in both the paraplegia group (t = 4.572, P = 0.000) and the tetraplegia group (t = 4.822, P = 0.000). Conclusions There are abnormalities in resting brain activation and functional connectivity of brain network after SCI, which are manifested as local enhancement of spontaneous neural activity in some brain regions and abnormal functional connectivity in cerebral cortices and brain regions. [ABSTRACT FROM AUTHOR]

Understanding the factors that influence nitrite degradation in whole blood and developing methods for its stable preservation are crucial for ensuring accurate and reliable forensic identification in cases of nitrite poisoning. This study systematically monitored nitrite degradation and changes in hemoglobin proportions across different initial nitrite concentrations and blood samples. It was revealed that high nitrite concentrations rapidly reduced deoxyhemoglobin levels within the first 15 minutes and subsequently reacted with oxyhemoglobin at a slower rate. Therefore, the proportions of these two hemoglobin forms are key factors in determining nitrite degradation rates. Regarding preservation, the study examined the effects of low temperatures (4°C and -20°C) and various preservatives (potassium ferricyanide, N-ethylmaleimide) on nitrite stability. The results indicate that adding 6.6 g/L potassium ferricyanide can rapidly eliminate all deoxyhemoglobin and reduce oxyhemoglobin proportions to below 60 %, enabling stable preservation of high nitrite concentrations in whole blood for over 30 days at -20°C. The efficacy of potassium ferricyanide was further validated in forensic-acquired postmortem heart blood samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To date our knowledge of skeletal muscle deoxygenation as measured by near-infrared spectroscopy (NIRS) is predicated almost exclusively on sampling of superficial muscle(s), most commonly the vastus lateralis (VL-s). Recently developed high power NIRS facilitates simultaneous sampling of deep (i.e., rectus femoris, RF-d) and superficial muscles of RF (RF-s) and VL-s. Because deeper muscle is more oxidative with greater capillarity and sustains higher blood flows than superficial muscle, we used time-resolved NIRS to test the hypotheses that, following exercise onset, the RF-d has slower deoxy[Hb+Mb] kinetics with reduced amplitude than superficial muscles. Thirteen participants performed cycle exercise transitions from unloaded to heavy work rates. Within the same muscle (RF-s vs. RF-d) deoxy[Hb+Mb] kinetics (mean response time, MRT) and amplitudes were not different. However, compared with the kinetics of VL-s, deoxy[Hb+Mb] of RF-s and RF-d were slower (MRT: RF-s, 51 ± 23; RF-d, 55 ± 29; VL-s, 18 ± 6 s; P  MRT-on (P

Diffuse optical spectroscopic imaging (DOSI) and diffuse correlation spectroscopy (DCS) are model-based near-infrared (NIR) methods that measure tissue optical properties (broadband absorption, ? a , and reduced scattering, ? s ? ) and blood flow (blood flow index, BFI), respectively. DOSI-derived ? a values are used to determine composition by calculating the tissue concentration of oxy- and deoxyhemoglobin ( HbO 2 , HbR), water, and lipid. We developed and evaluated a combined, coregistered DOSI/DCS handheld probe for mapping and imaging these parameters. We show that uncertainties of 0.3 ?? mm ? 1 (37%) in ? s ? and 0.003 ?? mm ? 1 (33%) in ? a lead to ? 53 % and 9% errors in BFI, respectively. DOSI/DCS imaging of a solid tissue-simulating flow phantom and

Multichannel functional near-infrared spectroscopy (fNIRS) is a tool used to capture changes in cerebral blood flow. A consistent result for depression is a decrease in blood flow in the frontal cortex leading to hypofrontality, which indicates multidomain functional impairment. Repetitive transcranial magnetic stimulation (rTMS) and elective convulsive therapy (ECT) are alternatives to antidepressant drugs for the treatment of depression but the underlying mechanism is yet to be elucidated. The aim of the current study was to evaluate cerebral blood flow using fNIRS following rTMS treatment in patients with depression. The cerebral blood flow of 15 patients with moderate depression after rTMS treatment was measured using fNIRS. While there was clear hypofrontality during pretreatment (5 ± 2.5), a notable increase in oxygenated hemoglobin was observed after 30 sessions with rTMS (50 ± 15). This increased blood flow was observed in a wide range of channels in the frontal cortex; however, the centroid values were similar between the treatments. Increased blood flow leads to the activation of neuronal synapses, as noted with other neuromodulation treatments such as electroconvulsive therapy. This study describes the rTMS-induced modulation of blood oxygenation response over the prefrontal cortex in patients with depression, as captured by fNIRS. Future longitudinal studies are needed to assess cerebral blood flow dynamics during rTMS treatment for depression. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects on prefrontal cortex brain activity when participants attempted to stop a car accurately at a stop line when driving at different speeds using functional near‐infrared spectroscopy (fNIRS). Twenty healthy subjects with driving experience drove their own cars for a distance of 60 m five times each at their own pace or as fast as possible. The variation in the distance between the stop line and the car was not significantly different between the self‐paced and high‐speed tasks. However, oxygenated hemoglobin concentration in the prefrontal cortex was significantly higher in the high‐speed task than in the self‐paced task. These findings suggest that driving at high speed requires more divided attention than driving at self‐paced speed, even though the participants were able to stop the car at the same distance from the target. This study shows the advantages and usefulness of fNIRS. [ABSTRACT FROM AUTHOR]

Genetic determinants of sleep-disordered breathing (SDB), a common set of disorders that contribute to significant cardiovascular and neuropsychiatric morbidity, are not clear. Overnight nocturnal oxygen saturation (SaO2) is a clinically relevant and easily measured indicator of SDB severity but its genetic contribution has never been studied. Our recent study suggests nocturnal SaO2 is heritable. We performed linkage analysis, association analysis and haplotype analysis of average nocturnal oxyhaemoglobin saturation in participants in the Cleveland Family Study (CFS), followed by gene-based association and additional tests in four independent samples. Linkage analysis identified a peak (LOD = 4.29) on chromosome 8p23. Follow-up association analysis identified two haplotypes in angiopoietin-2 (ANGPT2) that significantly contributed to the variation of SaO2 (P = 8 × 10-5) and accounted for a portion of the linkage evidence. Gene-based association analysis replicated the association of ANGPT2 and nocturnal SaO2. A rare missense SNP rs200291021 in ANGPT2 was associated with serum angiopoietin-2 level (P = 1.29 × 10-4), which was associated with SaO2 (P = 0.002). Our study provides the first evidence for the association of ANGPT2, a gene previously implicated in acute lung injury syndromes, with nocturnal SaO2, suggesting that this gene has a broad range of effects on gas exchange, including influencing oxygenation during sleep.

PurposeTime-resolved near-infrared spectroscopy was used to quantify tissue oxy- and deoxyhemoglobin concentrations ([HbO2] and [HbR]) and O2 saturation (stO2) in the oblique fibers of the vastus medialis muscle and brain prefrontal cortex during knee extension with and without blood flow restriction (BFR).MethodsSix young healthy males performed three sets of knee extensions on a dynamometer (50% one-repetition maximum) separated by 90-s rest periods in three conditions: 1) until fatigue without BFR (fatigue), 2) until fatigue with BFR (100 mm Hg cuff constriction around thigh (BFR)), 3) same number of repetitions from condition 2 without BFR (matched). Each condition was performed on a separate visit.ResultsBFR was associated with higher [HbR] at the oblique fibers of the vastus medialis muscle (rest 1: 57.8 (BFR) vs 35.0 μM (matched); P < 0.0001) and a significantly lower stO2 during recovery periods between sets (7.5%-11.2 % lower than non-BFR conditions for rest 1 and 2, P < 0.0001). Using a piecewise linear spline method, a spike in [HbR] was observed before the onset of HbR clearance during recovery, causing HbR clearance to begin at a higher concentration (81 (BFR) vs 62 μM (matched), P = 0.029). [HbO2] kinetics during recovery were also affected by BFR, with longer duration (BFR, 51 s; matched, 31 s; P = 0.047) but lower rate of increase (BFR, 58 μM·min; matched, 89 μM·min; P = 0.004) during recovery. In the prefrontal cortex, BFR was associated with increased [HbR], diminished increase in [HbO2], and higher subjective exertion.ConclusionsThese findings yield insight into possible physiological mechanisms of BFR and suggest a role of time-resolved near-infrared spectroscopy in monitoring and optimization of BFR exercise on an individual basis.

A major need exists for methods to assess organ oxidative metabolic states in vivo. By contrasting the responses to cyanide (CN) poisoning versus hemorrhage in animal models, we demonstrate that diffuse optical spectroscopy (DOS) can detect cytochrome c oxidase (CcO) redox states. Intermittent decreases in inspired O2 from 100% to 21% were applied before, during, and after CN poisoning, hemorrhage, and resuscitation in rabbits. Continuous DOS measurements of total hemoglobin, oxyhemoglobin, deoxyhemoglobin, and oxidized and reduced CcO from muscle were obtained. Rabbit hemorrhage was accomplished with stepwise removal of blood, followed by blood resuscitation. CN treated rabbits received 0.166  mg/min NaCN infusion. During hemorrhage, CcO redox state became reduced concurrently with decreases in oxyhemoglobin, resulting from reduced tissue oxygen delivery and hypoxia. In contrast, during CN infusion, CcO redox state decreased while oxyhemoglobin concentration increased due to CN binding and reduction of CcO with resultant inhibition of the electron transport chain. Spectral absorption similarities between hemoglobin and CcO make noninvasive spectroscopic distinction of CcO redox states difficult. By contrasting physiological perturbations of CN poisoning versus hemorrhage, we demonstrate that DOS measured CcO redox state changes are decoupled from hemoglobin concentration measurement changes.

BACKGROUND: The current diagnosis and study of depression lacks objective biological indicators. As an emerging non-invasive brain functional imaging technology, functional near infrared spectroscopy (fNIRS) may be a potential biomarker for the identification and diagnosis of depression. OBJECTIVE: To review the application of fNIRS technique in depression research and provide guidance for clinical research. METHODS: The keywords were “functional near-infrared spectroscopy, oxyhemoglobins, prefrontal cortex, depressive disorder.” The first author searched CNKI, WanFang, VIP, PuMed and Web of Science database from 1996 to 2020 in Chinese and English. Finally, 50 literatures were selected for review. RESULTS AND CONCLUSION: fNIRS signal may be a potential biomarker for depression. fNIRS technology is mainly used to study the cognitive dysfunction of depression based on the frontal lobe hemodynamic changes, which can be used for the differential diagnosis of depression. However, the current research on fNIRS is still in the exploratory stage, and there are still some defects in the existing research, which need to be further optimized and deepened in the future research. It can increase the study sample size and monitoring indicators, and integrate fNIRS with other technologies to improve the temporal and spatial resolution, so as to study the neural mechanism of depression systematically, comprehensively and accurately [ABSTRACT FROM AUTHOR]

There is a need for cost effective, quantitative tissue spectroscopy and imaging systems in clinical diagnostics and pre-clinical biomedical research. A platform that utilizes a commercially available light-emitting diode (LED) based projector, cameras, and scaled Monte Carlo model for calculating tissue optical properties is presented. These components are put together to perform spatial frequency domain imaging (SFDI), a model-based reflectance technique that measures and maps absorption coefficients (μa) and reduced scattering coefficients (μs') in thick tissue such as skin or brain. We validate the performance of the flexible LED and modulation element (FLaME) system at 460, 530, and 632 nm across a range of physiologically relevant μa values (0.07 to 1.5  mm-1) in tissue-simulating intralipid phantoms, showing an overall accuracy within 11% of spectrophotometer values for μa and 3% for μs'. Comparison of oxy- and total hemoglobin fits between the FLaME system and a spectrophotometer (450 to 1000 nm) is differed by 3%. Finally, we acquire optical property maps of a mouse brain in vivo with and without an overlying saline well. These results demonstrate the potential of FLaME to perform tissue optical property mapping in visible spectral regions and highlight how the optical clearing effect of saline is correlated to a decrease in μs' of the skull.

IntroductionAlthough various methods exist for monitoring flaps during reconstructive surgery, surgeons primarily rely on assessment of clinical judgment. Early detection of vascular complications improves rate of flap salvage. Spatial frequency domain imaging (SFDI) is a promising new technology that provides oxygenation images over a large field of view. The goal of this clinical pilot study is to use SFDI in perforator flap breast reconstruction.MethodsThree women undergoing unilateral breast reconstruction after mastectomy were enrolled for our study. The SFDI system was deployed in the operating room, and images acquired over the course of the operation. Time points included images of each hemiabdominal skin flap before elevation, the selected flap after perforator dissection, and after microsurgical transfer.ResultsSpatial frequency domain imaging was able to measure tissue oxyhemoglobin concentration (ctO2Hb), tissue deoxyhemoglobin concentration, and tissue oxygen saturation (stO2). Images were created for each metric to monitor flap status and the results quantified throughout the various time points of the procedure. For 2 of 3 patients, the chosen flap had a higher ctO2Hb and stO2. For 1 patient, the chosen flap had lower ctO2Hb and stO2. There were no perfusion deficits observed based on SFDI and clinical follow-up.ConclusionsThe results of our initial human pilot study suggest that SFDI has the potential to provide intraoperative oxygenation images in real-time during surgery. With the use of this technology, surgeons can obtain tissue oxygenation and hemoglobin concentration maps to assist in intraoperative planning; this can potentially prevent complications and improve clinical outcome.

Objectives: Age-related speech perception difficulties may be related to a decline in central auditory processing abilities, particularly in noisy or challenging environments. However, how the activation patterns related to speech stimulation in different noise situations change with normal aging has yet to be elucidated. In this study, we aimed to investigate the effects of noisy environments and aging on patterns of auditory cortical activation., Design: We analyzed the functional near-infrared spectroscopy signals of 20 young adults, 21 middle-aged adults, and 21 elderly adults, and evaluated their cortical response patterns to speech stimuli under five different signal to noise ratios (SNRs). In addition, we analyzed the behavior score, activation intensity, oxyhemoglobin variability, and dominant hemisphere, to investigate the effects of aging and noisy environments on auditory cortical activation., Results: Activation intensity and oxyhemoglobin variability both showed a decreasing trend with aging at an SNR of 0 dB; we also identified a strong correlation between activation intensity and age under this condition. However, we observed an inconsistent activation pattern when the SNR was 5 dB. Furthermore, our analysis revealed that the left hemisphere may be more susceptible to aging than the right hemisphere. Activation in the right hemisphere was more evident in older adults than in the left hemisphere; in contrast, younger adults showed leftward lateralization., Conclusions: Our analysis showed that with aging, auditory cortical regions gradually become inflexible in noisy environments. Furthermore, changes in cortical activation patterns with aging may be related to SNR conditions, and that understandable speech with a low SNR ratio but still understandable may induce the highest level of activation. We also found that the left hemisphere was more affected by aging than the right hemisphere in speech perception tasks; the left-sided dominance observed in younger individuals gradually shifted to the right hemisphere with aging., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Ear & Hearing is published on behalf of the American Auditory Society, by Wolters Kluwer Health, Inc.)

Background: Pulse oximetry uses noninvasive optical measurements of light transmission from each of two sources through vascularised living tissue over the cardiac cycle (SpO 2 ). From those measurements, the relative amount of oxygenated haemoglobin (SaO 2 ) in circulating blood can be deduced. Recent reports have shown that, compared with SaO 2 measurements from blood samples, SpO 2 measurements are biased erroneously high for patients with dark skin., Methods: We developed a new method, spectrally resolved photoplethysmography (srPPG), to examine how spectral bandwidth affects the transmission of polychromatic light through the fingertip across the cardiac cycle. We measured and recorded the spectral transmission through the fingertip as the O 2 concentration in inspired air was reduced. We applied digital spectral filters of two different bandwidths, narrow or broad, to the same srPPG recordings to determine whether SpO 2 readings systematically varied for the two bandwidths. The srPPG method also allowed us to measure the fractional amount of melanin in the optical path. The effect of melanin content on the ratio of SpO 2 readings for narrow and broad spectral bandwidths was analysed., Results: We hypothesised, based upon the Beer-Lambert law, and then showed experimentally, that the light emission spectra of light-emitting diode light sources, as used in commercial pulse oximeters, result in erroneously high SpO 2 measurements for patients having greater melanin concentrations in their skin than those of the subject pool used for instrument calibration., Conclusions: To eliminate melanin bias, pulse oximeters should use much narrower spectral bandwidths than those used in current models., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Subarachnoid hemorrhage (SAH) is a neurological disorder that severely damages the brain and causes cognitive impairment. MicroRNAs are critical regulators in a variety of neurological diseases. MiR-497-5p has been found to be downregulated in the aneurysm vessel walls obtained from patients with aneurysmal subarachnoid hemorrhage, but its functions and mechanisms in SAH have not been reported. Therefore, this study was designed to investigate the effect of miR-497-5p and its related mechanisms in SAH. We established an in vitro SAH model by exposing PC12 cells to oxyhemoglobin (oxyHb). We found that miR-497-5p was downregulated in SAH serum and oxyHb-treated PC12 cells, and its overexpression inhibited the oxyHb-induced apoptosis, inflammatory response and oxidative stress via activation of the Nrf2 pathway. Mechanistically, the targeting relationship between miR-497-5p and Otx1 was verified by luciferase reporter assays. Moreover, Otx1 upregulation abolished the protective effects of miR-497-5p upregulation against oxyHb-induced apoptosis, inflammation and oxidative stress in PC12 cells. Collectively, our findings indicate that miR-497-5p could inhibit the oxyHb-induced SAH damage by targeting Otx1 to activate the Nrf2/HO-1 pathway, which provides a potential therapeutic target for SAH treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective . Intracortical microstimulation (ICMS) can be an effective method for restoring sensory perception in contemporary brain-machine interfaces. However, the mechanisms underlying better control of neuronal responses remain poorly understood, as well as the relationship between neuronal activity and other concomitant phenomena occurring around the stimulation site. Approach . Different microstimulation frequencies were investigated in vivo on Thy1-GCaMP6s mice using widefield and two-photon imaging to evaluate the evoked excitatory neural responses across multiple spatial scales as well as the induced hemodynamic responses. Specifically, we quantified stimulation-induced neuronal activation and depression in the mouse visual cortex and measured hemodynamic oxyhemoglobin and deoxyhemoglobin signals using mesoscopic-scale widefield imaging. Main results . Our calcium imaging findings revealed a preference for lower-frequency stimulation in driving stronger neuronal activation. A depressive response following the neural activation preferred a slightly higher frequency stimulation compared to the activation. Hemodynamic signals exhibited a comparable spatial spread to neural calcium signals. Oxyhemoglobin concentration around the stimulation site remained elevated during the post-activation (depression) period. Somatic and neuropil calcium responses measured by two-photon microscopy showed similar dependence on stimulation parameters, although the magnitudes measured in soma was greater than in neuropil. Furthermore, higher-frequency stimulation induced a more pronounced activation in soma compared to neuropil, while depression was predominantly induced in soma irrespective of stimulation frequencies. Significance . These results suggest that the mechanism underlying depression differs from activation, requiring ample oxygen supply, and affecting neurons. Our findings provide a novel understanding of evoked excitatory neuronal activity induced by ICMS and offer insights into neuro-devices that utilize both activation and depression phenomena to achieve desired neural responses., (Creative Commons Attribution license.)

This study investigated brain responses during cybersickness in healthy adults using functional near-infrared spectroscopy (fNIRS). Thirty participants wore a head-mounted display and observed a virtual roller coaster scene that induced cybersickness. Cortical activation during the virtual roller coaster task was measured using fNIRS. Cybersickness symptoms were evaluated using a Simulator Sickness Questionnaire (SSQ) administered after the virtual rollercoaster. Pearson correlations were performed for cybersickness symptoms and the beta coefficients of hemodynamic responses. The group analysis of oxyhemoglobin (HbO) and total hemoglobin (HbT) levels revealed deactivation in the bilateral angular gyrus during cybersickness. In the Pearson correlation analyses, the HbO and HbT beta coefficients in the bilateral angular gyrus had a significant positive correlation with the total SSQ and disorientation. These results indicated that the angular gyrus was associated with cybersickness. These findings suggest that the hemodynamic response in the angular gyrus could be a biomarker for evaluating cybersickness symptoms., (© 2024. The Author(s).)

Background and objectiveObjective methods to assess port wine stain (PWS) response to laser treatment have been the subject of various research efforts for several years. Herein, we present a pilot study using a newly developed, light emitting diode (LED) based spatial frequency domain imaging (SFDI) device to record quantitatively biochemical compositional changes in PWS after laser therapy.Study design/patients and methodsA SFDI system was used to image before, and after, five PWS treatment sessions [n = 4 subjects (one subject was imaged before and after two consecutive laser treatments)]. SFDI derived wide-field optical properties (absorption and scattering) and tissue chromophore concentrations including oxy-hemoglobin (ctO(2) Hb), deoxy-hemoglobin (ctHHb), total hemoglobin (ctTHb), and tissue oxygen saturation (stO(2) ) are presented for skin imaged prior to and immediately after laser treatment. The SFDI derived images were analyzed by comparing the above measurements in PWS to those of normal skin and tracking changes immediately after laser exposure.ResultsElevated oxy-hemoglobin (>20%) and tissue oxygen saturation (>5%) were measured in all PWS lesions and compared to values for normal skin prior to treatment. Laser treatment resulted in an increase in deoxy-hemoglobin (>100%), decrease in tissue oxygen saturation (>10%), and reduced scattering (>15%) in all PWS lesions. One subject was followed before and after two consecutive laser treatments and the overall improvement in PWS lesion blanching was quantitatively assessed by measuring a 45% decrease in dermal blood volume.ConclusionSFDI is a rapid non-contact wide-field optical technique that shows potential as an imaging device that can be used to quantify biochemical compositional changes in PWS after laser therapy. Future work will investigate the potential of SFDI to provide intra-operative guidance for laser therapy of PWS lesions on an individual patient basis.

Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

Approximately 8-20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.

Oxygenation measurements are widely used in patient care. However, most clinically available instruments currently consist of contact probes that only provide global monitoring of the patient (e.g., pulse oximetry probes) or local monitoring of small areas (e.g., spectroscopy-based probes). Visualization of oxygenation over large areas of tissue, without a priori knowledge of the location of defects, has the potential to improve patient management in many surgical and critical care applications. In this study, we present a clinically compatible multispectral spatial frequency domain imaging (SFDI) system optimized for surgical oxygenation imaging. This system was used to image tissue oxygenation over a large area (16×12 cm) and was validated during preclinical studies by comparing results obtained with an FDA-approved clinical oxygenation probe. Skin flap, bowel, and liver vascular occlusion experiments were performed on Yorkshire pigs and demonstrated that over the course of the experiment, relative changes in oxygen saturation measured using SFDI had an accuracy within 10% of those made using the FDA-approved device. Finally, the new SFDI system was translated to the clinic in a first-in-human pilot study that imaged skin flap oxygenation during reconstructive breast surgery. Overall, this study lays the foundation for clinical translation of endogenous contrast imaging using SFDI.

BackgroundThe purpose of this study was to investigate the capabilities of a novel optical wide-field imaging technology known as spatial frequency domain imaging to quantitatively assess reconstructive tissue status.MethodsTwenty-two cutaneous pedicle flaps were created on 11 rats based on the inferior epigastric vessels. After baseline measurement, all flaps underwent vascular ischemia, induced by clamping the supporting vessels for 2 hours (either arteriovenous or selective venous occlusions); normal saline was injected into the control flap and hypertonic-hyperoncotic saline solution was injected into the experimental flap. Flaps were monitored for 2 hours after reperfusion. The spatial frequency domain imaging system was used for quantitative assessment of flap status over the duration of the experiment.ResultsAll flaps demonstrated a significant decline in oxyhemoglobin and tissue oxygen saturation in response to occlusion. Total hemoglobin and deoxyhemoglobin were increased markedly in the selective venous occlusion group. After reperfusion and the administration of solutions, oxyhemoglobin and tissue oxygen saturation in those flaps that survived gradually returned to baseline levels. However, flaps for which oxyhemoglobin and tissue oxygen saturation did not show any signs of recovery appeared to be compromised and eventually became necrotic within 24 to 48 hours in both occlusion groups.ConclusionsSpatial frequency domain imaging technology provides a quantitative, objective method of assessing tissue status. This study demonstrates the potential of this optical technology to assess tissue perfusion in a very precise and quantitative way, enabling wide-field visualization of physiologic parameters. The results of this study suggest that spatial frequency domain imaging may provide a means for prospectively identifying dysfunctional flaps well in advance of failure.

We describe the development of a non-invasive method for quantitative tissue temperature measurements using Broadband diffuse optical spectroscopy (DOS). Our approach is based on well-characterized opposing shifts in near-infrared (NIR) water absorption spectra that appear with temperature and macromolecular binding state. Unlike conventional reflectance methods, DOS is used to generate scattering-corrected tissue water absorption spectra. This allows us to separate the macromolecular bound water contribution from the thermally induced spectral shift using the temperature isosbestic point at 996 nm. The method was validated in intralipid tissue phantoms by correlating DOS with thermistor measurements (R=0.96) with a difference of 1.1+/-0.91 degrees C over a range of 28-48 degrees C. Once validated, thermal and hemodynamic (i.e. oxy- and deoxy-hemoglobin concentration) changes were measured simultaneously and continuously in human subjects (forearm) during mild cold stress. DOS-measured arm temperatures were consistent with previously reported invasive deep tissue temperature studies. These results suggest that DOS can be used for non-invasive, co-registered measurements of absolute temperature and hemoglobin parameters in thick tissues, a potentially important approach for optimizing thermal diagnostics and therapeutics.

Diffuse optical spectroscopy (DOS), which is used to image tumor metabolic response to neoadjuvant chemotherapy (NAC), shows large changes in tumor functional parameters with significant reductions in oxy- and deoxyhemoglobin for responders versus nonresponders. Although investigational, DOS may provide a cost-effective, risk-free method for optimizing NAC drug and dosing strategies for individual patients.

Study objectiveExposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B(12)) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigate the use of intramuscular cobinamide sulfite to reverse cyanide toxicity-induced physiologic changes in a sublethal cyanide exposure animal model and determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity.MethodsNew Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous-wave near-infrared spectroscopy monitoring of tissue oxyhemoglobin and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5).ResultsIntramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and within deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system occurred within a mean of 1,032 minutes in the control group and 9 minutes in the cobinamide group, with a difference of 1,023 minutes (95% confidence interval 116 to 1,874 minutes). In muscle tissue, recovery times were 76 and 24 minutes, with a difference of 52 minutes (95% confidence interval 7 to 98 minutes). RBC cyanide levels returned toward normal significantly faster in cobinamide sulfite-treated animals than in control animals.ConclusionIntramuscular cobinamide sulfite rapidly and effectively reverses the physiologic effects of cyanide poisoning, suggesting that a compact cyanide antidote kit can be developed for mass casualty cyanide exposures.

Our purpose is to compare cobinamide to hydroxocobalamin in reversing cyanide (CN)-induced physiologic effects in an animal model using diffuse optical spectroscopy (DOS). Cyanide poisoning is a major threat worldwide. Cobinamide is a novel molecule that can bind two molecules of cyanide, has a much higher binding affinity than hydroxocobalamin, and is more water soluble. We investigated the ability of equimolar doses of cobinamide and hydroxocobalamin to reverse the effects of cyanide exposure in an animal model monitored continuously by DOS. Cyanide toxicity was induced in 16 New Zealand white rabbits by intravenous infusion. Animals were divided into three groups: controls (n=5) received saline following cyanide, hydroxocobalamin (N=6) following cyanide, and cobinamide (N=5) following cyanide. Cobinamide caused significantly faster and more complete recovery of oxy- and deoxyhemoglobin concentrations in cyanide-exposed animals than hydroxocobalamin- or saline-treated animals, with a recovery time constant of 13.8+/-7.1 min compared to 75.4+/-25.1 and 76.4+/-42.7 min, for hydroxocobalamin- and saline-treated animals, respectively (p

We present a novel, noncontact method for the determination of quantitative optical properties of turbid media from 430 to 1050 nm. Through measuring the broadband reflectance from an unknown sample as a function of the spatial frequency of the projected illumination patterns, the absolute absorption and reduced scattering coefficients can be calculated without a priori assumptions of the chromophores present. This technique, which is called spatially modulated quantitative spectroscopy (SMoQS), was validated through the quantification of optical properties of homogenous liquid phantoms with known concentrations of absorbers and scatterers. The properties of the phantoms were recovered across the range of values prepared with R(2) values of 0.985 and 0.996 for absorption and reduced scattering, respectively. A measurement was also performed on skin tissue as a demonstration of the method's performance in vivo. The resultant absorption spectrum was well described by a multichromophore fit, and the quantitative values for oxy- and deoxyhemoglobin, water, and melanin were within published ranges for skin.