Near-infrared Spectroscopy Probes Research Articles

Influence of umbilical cord clamping time on cerebral oxygenation and early cardiac function in term infants.

Delayed cord clamping is the standard of care for both term and preterm infants worldwide. The aim of this study was to evaluate the effect of 60-second or 180-second delayed cord clamping during labor on cerebral oxygenation and cardiac function. Healthy newborns were divided into two groups: a 60-second delay in cord clamping (60-s DCC) and a 180-second delay in cord clamping (180-s DCC) at birth. Pulse oximetry and cerebral near-infrared spectroscopy (cNIRS) probes were placed during postnatal care. A total of 84 healthy newborns were included in this study. Preductal oxygen saturation (SpO2), heart rate, and cNIRS values were recorded at 5 and 10 minutes after delivery. The cardiac function of the infants was assessed by echocardiography at 3-7 days postnatally. There was no significant difference between the groups in SpO2 and cNIRS values at 5 and 10 min. While there was no significant difference in the number of neonates with targeted SpO2 at the 5th and 10th min and targeted cNIRS values at the 10th min, there was a significant difference in the number of neonates with target cNIRS values at the 5th min between groups (p < 0.001). Echocardiographic findings showed that pulmonary flow velocity was increased in the 180-s DCC group; the difference was statistically significant (p = 0.04). Our results showed that the number of infants with normal cNIRS values regarding cerebral oxygenation was higher in the 180-s DCC group. The pulmonary flow velocity was significantly increased in the 180-s DCC group in terms of echocardiographic findings.

Prospective single-center study on the reliability of ipsilateral cerebral oximetry using near-infrared spectroscopy as a predictor for selective shunting during carotid endarterectomy.

Many techniques are available for the intraoperative assessment of brain perfusion during carotid endarterectomy, such as carotid stump pressure, near-infrared spectroscopy, somatosensory evoked potentials, transcranial Doppler, electroencephalography, and clinical assessment. The decision for selective carotid shunt insertion is dependent on clinical deterioration or the detection of cerebral hypoperfusion after cross-clamping of the internal carotid artery. Monitoring cerebral oximetry using near-infrared spectroscopy is a noninvasive technique for cerebral oxygen saturation measurement, reflecting changes in cerebral blood flow during carotid endarterectomy. The aim of this study was to evaluate the reliability of near-infrared spectroscopy as a predictor of selective shunting during carotid endarterectomy. In total, 47 conventional carotid endarterectomy surgeries were performed at our hospital between March 2016 and December 2021. All surgeries were performed under a regional cervical block supplemented with local infiltration anesthesia. All patients were monitored by cerebral oximetry using bilateral near-infrared spectroscopy probes and clinical assessment through communication with the patient (numerical, visual, and verbal) to indicate a selective shunt. Near-infrared spectroscopy values were recorded before and after internal carotid cross-clamping and after declamping. Any decrease in ipsilateral cerebral oximetry-near-infrared spectroscopy values equal to or more than 20% from the pre-clamping baseline reading associated with deterioration in neurological status (hemiparesis, aphasia, or deterioration in level of consciousness) after internal carotid artery cross-clamping was considered an indication for intraluminal carotid shunting. After internal carotid artery cross-clamping, 5 of 47 patients (10.6%) developed a significant drop in cerebral oxygen saturation associated with obvious clinical assessment deterioration in verbal communication and weakness in contralateral arm power. A Pruitt-Inahara carotid shunt was subsequently inserted, and 42 patients remained stable throughout surgery. The average decline in ipsilateral near-infrared spectroscopy values was 23.8% in patients with clinical deterioration. The average decline was 8.6% in patients who remained stable. Monitoring ipsilateral cerebral oximetry using near-infrared spectroscopy is an easy and reliable method for indicating selective shunting during carotid endarterectomy. A 20% decrease in ipsilateral brain tissue oximetry after internal carotid artery cross-clamping provides a reliable cut-off value for selective intraluminal carotid shunting during carotid endarterectomy.

Longitudinal Characterization of Hemodynamic Changes with Multimodal Optical Techniques in Patients with Sickle Cell Disease Treated with Mitapivat

The physiological impacts of sickle cell disease (SCD) are widespread and severe if left untreated. Sickled RBCs initiate vaso-occlusion (VOC) and have altered biomechanical properties that negatively affect blood rheology and microvascular hemodynamics in patients with SCD. Therapeutics can target different mechanistic pathways including reduction of hemoglobin S (HbS) polymerization, oxidative stress, or inflammation. There is an unmet need for non-invasive, point-of-care technologies that characterize the microvascular hemodynamics in SCD which could potentially broaden understanding of the underlying pathophysiology and supplement a clinician's ability to monitor therapeutic changes. Current clinical approaches can be time- and resource- intensive which limit their accessibility. Near-infrared spectroscopy (NIRS) is a non-invasive, optical technique that quantifies microvascular hemodynamics including hemoglobin (Hb) concentration, tissue oxygen saturation (StO 2), and blood flow (Cerussi et al, 2005). We evaluate the sensitivity of NIRS technologies to hemodynamic changes in patients with SCD undergoing treatment with mitapivat, an investigational oral allosteric activator of pyruvate kinase (PK), and compare the optical changes to changes in standard hematology markers with regard to the initial response and consistency of the response over time. Fifteen patientswith HbSSwere enrolled in a study (ClinicalTrials.gov, NCT04610866) evaluating the long-term safety and tolerability of mitapivat in patients with SCD. We performed an optical hemodynamic assessment for each patient for a total of eight study visits over the span of a year including at baseline prior to drug initiation. NIRS probes were affixed to the forearm and forehead to collect hemodynamic information characteristic of brain and skeletal muscle while performing a brachial cuff occlusion challenge. We quantified concentration of oxy- and deoxy- Hb as well as StO 2 during the resting baseline prior to the occlusion. Additionally, we analyzed the post-occlusion reactive hyperemic response to assess vascular reactivity. Analysis was focused on quantifying the degree of change due to mitapivat treatment as well as the consistency of the response over the course of a year. Optical metrics were first compared against changes in Hb (Quang et, 2022) and then evaluated for consistency throughout the rest of the study period. Nine out of 15 patients were assessed as baseline NIRS data were not available for six patients.We calculated optical hemodynamic metrics for all 72 measurement visits; two visits were excluded due to poor NIRS data quality. Figure 1A shows a typical measurement setup with NIRS probes acquiring simultaneous measurements from the forehead and forearm. Figure 1B compares the mean Hb level, mean forehead StO 2, and mean forearm StO 2 across the first year of treatment. Over the first six months, we observed an increase in forehead StO 2 from 56% to 60% and forearm StO 2 from 59% to 63%; blood Hb levels exhibited a similar increase going from 8.5 g/dL to 9.8 g/dL; this increase was sustained over the second six months for all three parameters. Average forehead StO 2 remained +3.6% above baseline while forearm StO 2 remained +1.7% above baseline at the end of a year. NIRS can non-invasively provide objective measures of tissue composition, metabolism and vascular reactivity and can be performed in a simple manner with a series of simple perturbations.In this limited dataset, we have demonstrated that NIRS appears to reflect changes in Hb related to mitapivat both in response to an acute change and over an extended period. Furthermore, we observed that on average, the NIRS responses were consistently elevated throughout the course of the year, mirroring what was observed in the blood Hb levels. Hemodynamic changes appear to be more easily observed in the brain rather than the skeletal muscle. Our data suggest that NIRS could be an adjunct for non-invasive hemodynamic monitoring in patients with SCD undergoing treatment.

Self-calibrated pulse oximetry algorithm based on photon pathlength change and the application in human freedivers.

Pulse oximetry estimates the arterial oxygen saturation of hemoglobin () based on relative changes in light intensity at the cardiac frequency. Commercial pulse oximeters require empirical calibration on healthy volunteers, resulting in limited accuracy at low oxygen levels. An accurate, self-calibrated method for estimating is needed to improve patient monitoring and diagnosis. Given the challenges of calibration at low levels, we pursued the creation of a self-calibrated algorithm that can effectively estimate across its full range. Our primary objective was to design and validate our calibration-free method using data collected from human subjects. We developed an algorithm based on diffuse optical spectroscopy measurements of cardiac pulses and the modified Beer-Lambert law (mBLL). Recognizing that the photon mean pathlength () varies with related absorption changes, our algorithm aligns/fits the normalized (across wavelengths) obtained from optical measurements with its analytical representation. We tested the algorithm with human freedivers performing breath-hold dives. A continuous-wave near-infrared spectroscopy probe was attached to their foreheads, and an arterial cannula was inserted in the radial artery to collect arterial blood samples at different stages of the dive. These samples provided ground-truth via a blood gas analyzer, enabling us to evaluate the accuracy of estimation derived from the NIRS measurement using our self-calibrated algorithm. The self-calibrated algorithm significantly outperformed the conventional method (mBLL with a constant ratio) for estimation through the diving period. Analyzing 23 ground-truth data points ranging from 41% to 100%, the average absolute difference between the estimated and the ground truth is for our algorithm, significantly lower than the observed with the conventional approach. By factoring in the variations in the spectral shape of relative to , our self-calibrated algorithm enables accurate estimation, even in subjects with low levels.

IMPACT OF HIGH-DOSE VASOPRESSOR DURING ENDOTOXIC SHOCK ON THE CEREBRAL, LINGUAL, HEPATIC, AND RENAL MICROCIRCULATION EVALUATED BY NEAR-INFRARED SPECTROSCOPY IN SWINE.

Background: High-dose vasopressors maintain blood pressure during septic shock but may adversely reduce microcirculation in vital organs. We assessed the effect of high-dose norepinephrine and vasopressin on the microcirculation of the brain, tongue, liver, and kidney during endotoxic shock using near-infrared spectroscopy (NIRS). Methods: Thirteen pigs (24.5 ± 1.8 kg) were anesthetized, and an NIRS probe was attached directly to each organ. Approximately 0.2, 0.5, 1, and 2 μg/kg/min of norepinephrine were administered in a stepwise manner, followed by 0.5, 1, 2, and 5 μg/kg/min of sodium nitroprusside in normal condition. Moreover, 1 μg/kg/h of lipopolysaccharide was administered continuously after 100 μg bolus to create endotoxic shock and after 1,000 mL of crystalloid infusion and high-dose norepinephrine (2, 5, 10, and 20 μg/kg/min) and vasopressin (0.6, 1.5, 3, and 6 U/min) were administered in a stepwise manner. The relationship between the MAP and each tissue oxygenation index (TOI) during vasopressor infusion was evaluated. Results: Three pigs died after receiving lipopolysaccharides, and 10 were analyzed. An increase of >20% from the baseline MAP induced by high-dose norepinephrine during endotoxic shock reduced the TOI in all organs except the liver. The elevation of MAP to baseline with vasopressin alone increased the kidney and liver TOIs and decreased the tongue TOI. Conclusion: Forced blood pressure elevation with high-dose norepinephrine during endotoxic shock decreased the microcirculation of vital organs, especially the kidney. Cerebral TOI may be useful for identifying the upper limit of blood pressure, at which norepinephrine impairs microcirculation.

Use of Near-InfraRed Spectroscopy (NIRS) during Vascular Occlusion Test (VOT) for predicting an increase in oxygen consumption after fluid challenge in circulatory shock patients

Background: The goal of fluid challenge (FC) is to increase cardiac output (CO) and oxygen delivery (DO2) (known as fluid responders) to correct tissue hypoxia. To optimize fluid administration, fluid challenge (FC) during dependence of oxygen consumption on oxygen delivery (VO2/DO2 dependency) would correct tissue hypoxia confirmed by an increase of oxygen consumption (VO2) and oxygen delivery (DO2) after FC (known as VO2 responders) and get more benefit from a reduction in tissue hypoxia. Markers of anaerobic metabolisms, such as blood lactate concentration or the ratio of venous-arterial CO2 tension difference (P(cv-a)CO2) over arterial-to-venous oxygen content difference (C(a-cv)O2), can predict VO2 responders but still have several limitations. Therefore, near-infrared spectroscopy (NIRS) has been developed to evaluate tissue perfusion, presented as tissue oxygen saturation (StO2), at the bedside. Combining StO2 with the vascular occlusive test (VOT) and introducing a short period of forearm ischemia is a non-invasive technique to examine microvascular alterations at the bedside. However, a study validating the ability of these variables to predict VO2 response has not been conducted. Methods: We plan to conduct a single-center prospective study on circulatory failure patients. The cardiac index (CI), oxygen delivery (DO2), oxygen consumption (VO2), arterial lactate, central venous oxygen saturation (ScvO2), ratio of venous-arterial carbon dioxide tension to arterial-to-central venous oxygen content difference (P(cv-a)CO2/ C(a-cv)O2), and tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) probe during vascular occlusion test variables (NIRS-VOT variables) will be collected before and after the fluid challenge. Hypothesis: We hypothesize that markers of reactive hyperemia by NIRs will predict an increase in VO2 after FC in patients with circulatory shock. Ethics: The study protocol has been approved by the ethics committee of the faculty of medicine, Ramathibodi Hospital, Mahidol University (COA. MURA2022/80).

Performance of Near-Infrared Spectroscopy in Detecting Acute Tourniquet-Induced Upper-Extremity Ischemia Across Different Skin Phenotypes

Diagnosing acute tissue ischemia is challenging, particularly in patients with higher skin melanin content. We investigated whether near-infrared spectroscopy (NIRS) is effective and consistent in detecting upper extremity ischemia across various skin phenotypes. Volunteers underwent tourniquet-induced upper extremity ischemia. Skin color was evaluated by the Fitzpatrick scale (FP, range: I-VI) and the Von Luschan scale (vL, range: 1-36). A NIRS probe was placed on one finger. The tourniquet was inflated to 250 mmHg and perfusion was restricted for 7 minutes, followed by a 10-minute monitored reperfusion period. The percent tissue oxygenation (StO2) was recorded. A total of 55 volunteers were enrolled (22 self-identified as Caucasian, 21 African American, 7 Asian, 2 Latinx, and 2 Biracial). Average starting and ending StO2 for the cohort was 72.2% and 45.9%, respectively. However, there was variability based on skin melanin content. Increasing vL correlated with lower starting StO2, smaller StO2 decrease, and shorter time to reach ischemic steady state. High skin melanin (FP scale IV-VI) was associated with significantly lower starting StO2 (-7.1%) and shorter time to reach ischemic steady state (-0.3 mins). African Americans had lower starting StO2 (-8.6%) and 7.8% lesser total StO2 decrease than other groups. NIRS can rapidly detect acute onset tissue ischemia in the upper extremity. However, given the lower starting StO2 and smaller total StO2 decrease after tourniquet-induced ischemia for patients with higher skin melanin, using NIRS for clinical detection of acute ischemia may be more challenging in these patients. These inconsistencies may limit use of NIRS clinically for spot identification of ischemia. Although NIRS has utility in tracking tissue oxygenation, variable performance with different skin melanin content raises concerns as to whether different cutoff/threshold levels are needed for different groups, and whether NIRS is reliable for spot checks in acute events.

Hemodynamic alterations response to Chinese acupuncture therapy monitored by a custom near-infrared spectroscopy probe with an open hole.

Traditional acupuncture, a popular traditional Chinese medicine (TCM) technique, has demonstrated potential in relieving various ailments' symptoms. However, its black-box feedback loop model has limited proper evaluation and use by unskilled practitioners. This study aimed to analyze hemodynamic signals around acupoints during acupuncture to identify significant parameter changes. We designed hollow near-infrared spectroscopy (NIRS) probes for real-time measurements during acupuncture at acupoints, monitoring oxy-hemoglobin (HbO), deoxy-hemoglobin (Hb), and blood volume (HbT) changes. Acupuncture was performed on the "Xuehai" acupoint in 17 healthy subjects, with NIRS measuring hemodynamic alterations. Results showed significant and consistent increases in Hb and HbT around the acupoint, returning to baseline values after needle removal. One case of fainting revealed a significant Hb increase and HbO decrease. Acupuncture may induce tissue vasodilation and enhance oxygen consumption. This research provides a potential explanation for acupuncture's mechanism and emphasizes NIRS's potential in TCM.

RSO2 Measurement Using NIRS for Lower-Limb Blood Flow Monitoring and Estimation of Safe Balloon Occlusion/Deflation Time in Patients with PAS Who Underwent PBOA during CS.

We examined the utility of regional oxygen saturation (rSO2) measurement using near-infrared spectroscopy (NIRS) for monitoring lower-limb blood flow and estimate the safe balloon occlusion/deflation time in patients with PAS who underwent prophylactic balloon occlusion of the abdominal artery (PBOA) during cesarean section (CS). During CS, the NIRS probes were positioned on either of the anterior tibial muscles. rSO2 was measured continuously during balloon occlusion/deflation. A cycle consisted of inflating the aortic balloon for 30 min and deflating it for 5 min. The rSO2 before/during balloon occlusion and after 5 min of balloon deflation were evaluated. Sixty-two lower limbs (fifteen women and data from 31 sessions of balloon inflation/deflation) were evaluated. rSO2 during balloon occlusion was significantly lower than rSO2 before balloon occlusion (57.9% ± 9.6% vs. 80.3% ± 6.0%; p < 0.01). There were no significant differences between rSO2 before balloon occlusion and rSO2 after 5 min of balloon deflation (80.3% ± 6.0% vs. 78.7% ± 6.6%; p = 0.07). Postoperatively, the lower limbs showed no ischemic symptoms. NIRS can assess lower-limb rSO2 during PBOA for PAS in real time to determine ischemia severity, duration, and recovery capacity.

Aortic stiffness and impairments in cerebrovascular function in cancer survivorship

An established consequence of anti-cancer treatment is increased aortic stiffness, which impairs the aortic damping of cardiac-generated pulsatile pressure and blood flow. These increased pulsations may result in vascular injury in the microcirculation of target end organs like the brain. The aim of the present study was to determine the ramifications of elevated aortic stiffness on cerebral macro- and microvascular pulsatility and autoregulatory function in cancer survivors. We hypothesized that cerebrovascular pulsatility would be enhanced, and cerebrovascular reactivity (CVR) to elevations in arterial CO 2 would be impaired, both in the large and small cerebral vessels in patients with a history of cancer and anti-cancer treatment versus healthy age- and sex-matched non-cancer controls. Aortic arch pulse wave velocity (aaPWV), a regional measure of stiffness in the proximal aorta, was calculated from echocardiographic views of the aortic valve and the descending aortic arch. Subjects then breathed room air for 60s followed by ~2 minutes of rebreathing with simultaneous collection of end-tidal pressure of CO 2 (P ET CO 2 ). Middle cerebral artery blood flow velocity (MCAv) was assessed using transcranial doppler. Oxygenated (oxy-[Hb]) and deoxygenated (deoxy-[Hb]) cerebral microvascular hemoglobin concentrations were monitored using two near-infrared spectroscopy probes placed over the prefrontal cortices. Pulsatility was assessed at baseline using Gosling’s Pulsatility Index (PI) for both the microvasculature and MCA. To account for changes in perfusion pressure, MAP was collected via finger plethysmography and cerebrovascular conductance indices were calculated for both oxy-[Hb] (CVCi oxy ) and MCAv (CVCi MCA ). CVR was calculated as the slope of CVCi oxy and CVCi MCA over P ET CO 2 during rebreathing. Six women were recruited (n = 3/group). Age was similar between the healthy non-cancer controls (HC) and patients with a history of cancer and anti-cancer treatment (CS) (31.0 ± 7 vs. 32.7 ± 13 years). Baseline ventilatory (P ET CO 2 ), central and cerebral hemodynamics were also similar (all p &gt; 0.05). aaPWV was significantly elevated in CS compared to HC (5.3 ± 0.6 vs. 3.1 ± 1.1 m/s, p = 0.04). Cerebral microcirculation PI in CS was significantly elevated (0.04 ± 0.01 vs. 0.02 ± 0.01, p = 0.02), but MCA PI was not different (p &gt; 0.05). CVR-CVCi oxy was impaired in CS (-3.6 ± 2.8 vs. 1.5 ± 0.5 nM·mmHg -1 /mmHg, p = 0.03), and CVR-CVCi MCA was similarly reduced (-0.05 ± 0.06 vs. 0.15 ± 0.01 mm/sec·mmHg -1 /mmHg, p &lt; 0.01). The increase in MAP during hypercapnia was similar between groups. Consistent with our hypothesis, both CVR-CVCi oxy and CVR-CVCi MCA were attenuated in patients with a history of anti-cancer treatment. Additionally, the microvascular pulsatility was greater in CS. This suggests an impaired cerebrovascular function, possibly related to increased transmission of pulsatility into the brain, in the years following cancer diagnoses and treatment. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Feasibility of Near-Infrared Spectroscopy for Monitoring Hemodynamic Changes in Patients with Sickle Cell Disease Treated with Mitapivat

Background: Continuous inflammation and vasculopathy underlies the pathology of sickle cell disease (SCD). Therapeutics intervening the different stages in the pathophysiological cascade - polymerization of hemoglobin S (HbS) and "sickling" of the red blood cells (RBCs), vaso-occlusion and inflammation- are under development. Sickled RBCs initiate vaso-occlusion and have altered biomechanical properties that impact the rheology and hemodynamics in patients with SCD. There is an unmet need for robust, compact technologies that can non-invasively characterize the microvascular hemodynamics in SCD. Such a tool would be a valuable adjunct for clinicians both for broadening understanding of as well as monitoring therapeutic changes. However current clinical approaches can be time- and resource- intensive which limit their utility. Near-infrared spectroscopy (NIRS) is a non-invasive, optical technique for quantifying microvascular hemodynamics including hemoglobin concentration, tissue oxygen saturation, and blood flow (Cerussi et al, 2005). Here, we evaluate the sensitivity of NIRS to hemodynamic changes in patients with SCD undergoing treatment with Mitapivat (AG-348), a pyruvate kinase activator under clinical development to determine how well NIRS parameters compare with standard hematology markers. Methods: We studied patients currently enrolled in a Phase I/II clinical trial (ClinicalTrials.gov, NCT04610866) that evaluates the long-term safety and tolerability of Mitapivat in the SCD population. We performed tissue hemodynamic assessments by affixing NIRS probes to the forearm and forehead of the subjects at baseline (prior to drug initiation) and over the course of three months of treatment with Mitapivat totaling five measurement visits per patient. The optical hemodynamic assessment consisted of resting baseline measurements followed by a brachial cuff occlusion and a recovery period. We acquired optical measures of hemodynamic markers, such as the concentration of oxy- and deoxy- hemoglobin and tissue oxygen saturation (StO2). Additionally, we calculated measures of vascular reactivity by analyzing the post-occlusion reactive hyperemic response. These metrics are compared for each patient across time to determine if there are any significant changes compared to baseline. Optical metrics were compared against changes in blood hemoglobin (Hb) level, an expected therapeutic effect of Mitapivat (Xu et al, 2022). Nine patients with complete NIRS data at baseline and spanning 3 months of Mitapivat were analyzed. Results: We calculated optical hemodynamic metrics for all 45 measurement visits; one visit was excluded due to poor NIRS data quality. Figure 1A shows a typical measurement setup with NIRS probes acquiring simultaneous measurements from the forehead and forearm, which reflect tissue hemodynamics in the prefrontal cortex and skeletal muscle respectively. Figure 1B compares the mean Hb level, mean forehead StO2, and mean forearm StO2 across the first three months of treatment. On average, forehead StO2 acquired by NIRS trended similarly to the Hb level acquired by blood draws over the first three months. We observed that 7/9 patients exhibited a sustained increase in blood Hb compared to baseline; the mean Hb increase for all patients compared to baseline was 1.2 g/dL at the end of three months. Similarly, forehead StO2 measured by NIRS also showed a similar, sustained increase. The mean forehead StO2 increase after three months compared to baseline was 4.0%. Discussion: We have demonstrated that NIRS could be a promising adjunct for non-invasively monitoring hemodynamics in patients with SCD undergoing treatment with Mitapivat. NIRS can provide objective measures of tissue composition and metabolism and vascular reactivity which can be performed in a simple, non-invasive measurement. Future analysis will include analyzing optical metrics of vascular reactivity and blood flow. While this initial cohort is small, the preliminary results are encouraging and warrant continued study into NIRS as a tool for monitoring hemodynamic changes promoted by other therapies for SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Non-Invasive Optical Characterization of Tissue Hemodynamics in Sickle Cell Patients Undergoing Treatment with Isoquercetin

Sickle Cell Disease (SCD) is an inherited hemoglobin disorder which causes a mutation in the β subunit of hemoglobin (HbA), thus producing hemoglobin S (HbS) (Williams and Thein, 2018). When HbS is deoxygenated, red blood cells (RBC) can polymerize, which promotes increased rigidity and microvascular occlusions. The presence of mutated HbS increases the likelihood of recurrent venous thromboembolism (VTE). There is an unmet need for real-time, non-invasive methods of assessing microvascular hemodynamics and endothelial dysfunction. Near-Infrared Spectroscopy (NIRS), is a non-invasive, optical technique which measures tissue absorption and scattering between 650-1100 nm in subcutaneous tissue. NIRS has the capability to quantitatively measure the concentration of oxy- and deoxy- hemoglobin as well as blood flow. To determine the sensitivity of NIRS to changes in hemodynamics in SCD patients, we evaluated a cohort of SCD patients undergoing treatment with Isoquercetin (IQ), a flavonoid antithrombotic agent, and correlated the findings with D-dimer, a marker for blood clot degradation. We recruited a sub-cohort of 17 of 46 patients participating in a randomized, double-blind, placebo-controlled trial of IQ and performed an optical hemodynamic assessment at baseline and 4 weeks post-treatment. We used the commercial, multi-modal NIRS device (MetaOx, ISS Inc) which combines frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS) to acquire optical markers of tissue composition and blood flow, respectively. NIRS testing included resting baseline measurements and a brachial cuff occlusion. As seen in Figure 1A, a blood pressure cuff was wrapped around the bicep and the NIRS probe was placed on the ipsilateral forearm muscle. The challenge consisted of a 3-minute baseline, 3-minute cuff occlusion at 200 mmHg, and a 3-minute recovery. The decay constant τc of the intensity autocorrelation function g2(τ), which is an indicator of the bulk displacement of scattering particles (i.e. RBCs) in the forearm, was fitted from the DCS data. We compared the mean τc during the last 30s of the occlusion to D-dimer levels for all 17 patients at baseline and at 4 weeks follow up. Following a data quality review, 8 patients had NIRS data for baseline and follow up visits. D-dimer levels were 1.875 mcg/mL ± 0.869 mcg/mL at baseline and 1.449 mcg/mL ± 0.874 mcg/mL at 4 weeks follow up. Among the 8 patients with good quality data, 5/8 showed an average decrease in τc by 0.424 ms at 4 weeks follow up and an average decrease in D-dimer levels by 0.768 mcg/mL. The patient in Figure 1B showed 42.0% decrease in τc and 46.6% decrease in D-dimer levels from baseline to 4 weeks follow up. 2/8 patients showed an increase in τc by an average of 0.139 ms and an average increase in D-dimer levels by 0.320 mcg/mL. 1/8 patient showed a decrease in the τc with no change in D-dimer levels. We found that 7/8 patients with baseline and follow up visits had matching trends between D-dimer levels and τc. As demonstrated, a larger τc signified less movement of scattering particles, such as RBCs, due to increased blood coagulation. The remaining 9/17 patients had data from one visit of acceptable quality and were excluded from this analysis. The results of this initial analysis demonstrate autocorrelation decay time could be a promising metric that is reflective of blood coagulation and rheology. While this analysis focused on the changes observed in optical blood flow markers, further work will be performed to both expand upon this analysis and to integrate the compositional data acquired from the FD-NIRS portion of the measurements. NIRS can potentially complement traditional blood biomarkers when assessing anti-thrombotic effects of SCD treatments, such as Isoquercetin. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Identification of Ischemic Stroke Condition Based on Hemodynamic Biomarkers

Ischemic stroke is a cerebral hemodynamic disorder that occurs due to the impairment of hemoglobin supply to the tissue, a leading cause of mortality around the world. This research focuses on detecting ischemic stroke conditions by adding new hemodynamic biomarker information to the proposed low-cost wearable point-of-care diagnostic near-infrared spectroscopy (NIRS) device. Consequently, a new protocol-based sequence of experiments has been carried out to detect the ischemic condition. First, a multichannel, multiwavelength, and multibiomarkers-based point-of-care NIRS system has been developed to accommodate these features onboard. A four-wavelength, six-optode channels-based NIRS probe has been designed such that the physiological noise gets minimized and covers 100 mm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times20$ </tex-math></inline-formula> mm area of tissue, for example, the frontal lobe of the brain, with near and far distance concept of optode channels. Infinite impulse response (IIR) filters have been used onboard to improve the signal-to-noise ratio (SNR) up to 58.17 dB of the measured biomarker signal. The proposed pipeline of in-vivo occlusion experimentation evoked the ischemic condition at various stages to validate the system performance and temporal characteristics of biomarkers. First, basic PPG signals have recorded to test the performance of the device against the standard PPG signal, then the device has been placed a little upward from the finger to the forearm, where forearm occlusion has been done to mimic the ischemic condition, and finally, the device has been moved further upward and placed at the frontal lobe to record the evoked ischemic biomarker’s response while blocking the carotid artery.

Positive Association between NIRS‐derived measures of Microvascular Reactivity and Mitochondrial Capacity in the Quadriceps and Hamstrings

BACKGROUNDDelivery of oxygen to the mitochondria is essential for oxidative phosphorylation and the production of ATP during rest and during muscle contraction. Despite widespread application of near infrared spectroscopy (NIRS), to our knowledge it has not been used to evaluate whether oxygen delivery to the mitochondria, as assessed by post‐ischemic reoxygenation parameters, is related to the oxidative capacity of the muscle.PURPOSETo determine the relation between microvascular reactivity and mitochondrial oxidative capacity in the knee joint musculature using NIRS.METHODSBilateral measurements of the vastus lateralis (VL) and medial hamstring (MH) muscles were taken in 14 moderate to highly active healthy adults (7M/7F, age: 22 ± 3 yrs, BMI: 21.3 ± 3.5 kg/m2, physical activity levels: 4190 ± 1324 MET minutes/week). Two NIRS probes (Portamon, Artinis) were secured over the respective muscle bellies, which collected data during a 30 second bout of surface electrical stimulation that caused an increase in metabolism followed by brief arterial occlusions to determine the metabolic rate of the muscle over time. A final resting metabolism measurement was taken 5 minutes after the arterial occlusions to obtain the time to half recovery of metabolic rate (NIRS k), which is a valid estimate of mitochondrial oxidative capacity. Microvascular reactivity was measured as 1) the 10‐second reoxygenation slope of the oxygen saturation signal (StO2) and 2) the half time to peak oxygenation following 5 minutes of arterial occlusion in each muscle.RESULTSThere was a significant positive association between NIRS kand the reoxygenation slope in both the VL (r = 0.64, p = 0.025) and the MH (r = 0.53, p = 0.049) muscles. NIRS kvalues were also positively associated with the time to half peak oxygenation in the VL (r = 0.65, p = 0.021) and the MH (r = 0.60, p = 0.026) muscles. There were no differences between the VL and MH muscles for NIRS kvalues (Mean ± SD: 1.78 ± 0.24 vs. 1.78 ± 0.33, p = 0.99), 10‐second reoxygenation slope (2.16 ± 0.84 vs. 1.99 ± 0.96, p = 0.65), and half time to peak oxygenation (8.4s ± 1.6 vs. 9.1s ± 2.2, p = 0.38).CONCLUSIONOur results suggest that microvascular reactivity is positively associated with the mitochondrial capacity of the knee joint musculature in this sample of healthy adults. Whether these associations exist in different clinical populations warrants future investigation.

The Effect of Continuous PEEP Administration during Surfactant Instillation on Cerebral Hemodynamics in Intubated Preterm Infants: A NIRS Study.

There is an ongoing debate about the best and comfortable way to administer surfactant. We hypothesized that uninterrupted respiratory support and continuous PEEP implementation while instilling surfactant via endotracheal tube (ETT) with side port will result in higher regional cerebral tissue oxygenation (rcSO2) and the alterations in cerebral hemodynamics will be minimal. Preterm infants who required intubation in the delivery room and/or in the first 24 hours of life with gestational age <32 were enrolled. Patients were intubated either via conventional ETT or ETT with side port (Vygon) with appropriate sizes. Following neonatal intensive care unit admission a near-infrared spectroscopy (NIRS) probe was placed on the forehead and each infant was started to be monitored with NIRS. In conventional ETT group, patients separated from the ventilator while surfactant was instilled. In ETT with side port group, respiratory support was not interrupted during instillation. Heart rate, oxygen saturation, rcSO2, cerebral fractional tissue oxygen extraction (cFTOE), and blood pressures were recorded. A total of 46 infants were analyzed. Surfactant was instilled with conventional ETT in 23 and ETT with side port in 23 infants. Birth weights (1,037 ± 238 vs. 1,152 ± 277 g) and gestational ages (28 ± 2.3 vs. 29 ± 1.6 weeks) did not differ between groups. During instillation of surfactant, rcSO2 levels [61.5 (49-90) vs. 70 (48-85)] and cFTOE levels 0.28 (0.10-0.44) vs. 0.23 (0.03-0.44)] were similar (p = 0.58 and 0.82, respectively). Interruption of respiratory support during surfactant instillation did not significantly alter the cerebral tissue oxygenation. These results did not support our hypothesis and should be confirmed with further studies. · Monitoring intracerebral oxygenation changes during surfactant administration with NIRS is feasible.. · The surfactant administration method does not significantly alter the cerebral oxygenation.. · Surfactant administration itself rather than the method caused a transient drop in cerebral NIRS readings..

MITOCHONDRIAL OXYGENATION DURING CARDIOPULMONARY BYPASS: A PILOT STUDY

Introduction Cardiopulmonary bypass (CPB) is used during cardiac-surgery and provides oxygenated blood to the tissues. Ensuring adequate oxygenation is essential for the preservation of organ function during CPB. Both hypoxia and hyperoxia result in undesired outcomes and a narrow window for optimal oxygenation exists. Current perioperative monitoring techniques are not always sufficient to monitor adequate oxygenation, especially in high-risk patients. Near-infrared spectroscopy (NIRS) tissue oxygen measurement (StO2) is widely used to monitor tissue oxygenation but responds slowly to change. However, the novel non-invasive COMET-monitor measures the mitochondrial oxygen tension (mitoPO2) in the epidermis using the enhanced mitochondrial Protoporphyrin IX Triplet State Lifetime Technique (PpIX-TSLT). The mitoPO2 reflects the local balance between oxygen supply and consumption and provides an insight into the microcirculatory system [1]. This pilot study investigates the correlation between mitoPO2 versus StO2 and varying hemodynamic conditions during CPB and the development of acute kidney injury (AKI). Methods This single center observational study examined 41 cardiac-surgery patients requiring CPB. Six-hours pre-operatively, patients received a 5-aminolevulinc acid plaster on the upper arm to facilitate the mitoPO2 measurements. After induction of anesthesia, both the COMET and INVOS measurements were executed in 5-minute intervals throughout the procedure. To compare mitoPO2 with StO2, NIRS probes were placed near the COMET probe. Post-operatively, both measurements were stopped simultaneously, and the patients were observed until discharge for the development of AKI. Results NIRS data was available for 31 of the 41 patients. The median mitoPO2 at the start of surgery was 63.5 [40.0 – 74.8] mmHg and significantly decreased (p Discussion In contrast to StO2, the mitoPO2 decreased significantly during CPB time. A hemodilution study in pigs also demonstrated that mitoPO¬2 is more likely to change than StO2, which reacted slowly to change. The mitoPO2 also significantly decreased during non-pulsatile flow and increased once pulsatile flow returned, whilst the StO2 did not. This highlights the sensitivity of mitoPO2 to detect circulatory and microvascular changes early through the analysis of oxygen delivery on a cellular level. Lastly, the association found between the AKI and the non-AKI group in time spent below a mitoPO2 of 20 mmHg must be further examined in a well powered study. However, it highlights the potential of this technique to be an early predictor of ischemia.

Intramuscular Near-Infrared Spectroscopy for Muscle Flap Monitoring in a Porcine Model.

Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe

IntroductionFemale sexual arousal disorder (FSAD) can be caused by the change in vaginal structure due to the decline of estrogen and one of the main symptoms is vaginal dryness. FSAD is a prevalent problem afflicting women all over the world and thus the interest is growing on the matter, but related studies of monitoring FSAD using a non-invasive optical method barely have been carried out. AimThis study aims to investigate the longitudinal changes in female sexual arousal response induced by apomorphine (APO) administration in the ovariectomized rat using near-infrared spectroscopy (NIRS) probe. MethodsTo elicit sexual arousal, APO was administered subcutaneously to animals (n = 6) before and after ovariectomy, and the changes in oxyhemoglobin (OHb), deoxyhemoglobin (RHb), total hemoglobin (THb) concentration, and temperature on the vaginal wall after APO administration were monitored bi-weekly for 8 weeks. Furthermore, estradiol hormone, vaginal secretion, and body weight have been measured for comparison with the results from vaginal hemodynamics. ResultsAPO administration caused the increase of vaginal OHb and RHb concentration but a decrease in temperature. The amplitude of OHb, RHb, and THb increase induced by APO gradually decreased over 8 weeks after ovariectomy while the decrease in vaginal temperature became profound. The level of estradiol and vaginal secretions also decreased over 8 weeks after ovariectomy, but bodyweight showed an increasing trend. ConclusionsA comparison between the parameters measured from the NIRS probe and the others (estradiol level, amount of vaginal secretion, and body weight) proved that the NIRS has the potential as a monitoring tool to evaluate female sexual arousal response.Jeong H, Lee HS, Seong M, et al. Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe. J Sex Med 2021;18:1328–1336.

Monitoreo en tiempo-real de la producción de xilitol en biorreactor con Candida tropicalis IEC5-ITV utilizando Espectroscopia de Infrarrojo Cercano (NIRS)

The use of Near-Infrared Spectroscopy (NIRS) and Chemometrics in-situ or in-line monitoring of xylitol fermentation process by Candida tropicalis IEC5-ITV was investigated in a bioreactor and in a complex analytical matrix. Xylose, xylitol, biomass and glycerol determinations were performed by a transflection fiber optic probe, immersed in the culture broth and connected to a Near-Infrared (NIR) process analyzer. The NIR spectra recorded between 800 and 2,200 nm, these NIR Spectra were pretreated using Savitzky-Golay smoothing and second derivative in order to perform a partial least squares regression (PLSR) and generate the calibration models. These calibration models were tested by external validation and then used to predict concentrations of xylitol fermentations in batch culture. The standard errors of calibration (SEC) and determination coefficients (R2) for xylose, xylitol, biomass and glycerol were 0.234 (R2 = 0.991), 0.220 (R2 = 0.999), 0.234 (R2 = 0.991) and 0.015 (R2 = 0.999) g/L and standard errors of prediction (SEP) were 1.771, 0.192, 0.011, 0.503 g/L, respectively. Calibration and validation criteria were defined and evaluated in order to generate robust and reliable models of a xylitol fermentation process. For validation models, SEV and SEP were &lt; 10 % of initial concentration of xylose and R2 &gt; 0.96 were obtained.&nbsp; These results indicate that in situ NIRS probe is suitable for real-time monitoring of xylitol production.

Measuring tibial hemodynamics and metabolism at rest and after exercise using near-infrared spectroscopy.

The bone vascular system is important, yet evaluation of bone hemodynamics is difficult and expensive. This study evaluated the utility and reliability of near-infrared spectroscopy (NIRS), a portable and relatively inexpensive device, in measuring tibial hemodynamics and metabolic rate. Eleven participants were tested twice using post-occlusive reactive hyperemia technique with the NIRS probes placed on the tibia and the medial gastrocnemius (MG) muscle. Measurements were made at rest and after 2 levels of plantarflexion exercise. The difference between oxygenated and deoxygenated hemoglobin signal could be reliably measured with small coefficients of variation (CV; range 5.7-9.8%) and high intraclass correlation coefficients (ICC; range 0.73-0.91). Deoxygenated hemoglobin rate of change, a potential marker for bone metabolism, also showed good reliability (CV range 7.5-9.8%, ICC range 0.90-0.93). The tibia was characterized with a much slower metabolic rate compared with MG (p< 0.001). While exercise significantly increased MG metabolic rate in a dose-dependent manner (all p< 0.05), no changes were observed for the tibia after exercise compared with rest (all p> 0.05). NIRS is a suitable tool for monitoring hemodynamics and metabolism in the tibia. However, the local muscle exercise protocol utilized in the current study did not influence bone hemodynamics or metabolic rate. Novelty: NIRS can be used to monitor tibial hemodynamics and metabolism with good reliability. Short-duration local muscle exercise increased metabolic rate in muscle but not in bone. High level of loading and exercise volume may be needed to elicit measurable metabolic changes in bone.