Near-infrared Diffuse Correlation Spectroscopy Research Articles

How does obstructive sleep apnea alter cerebral hemodynamics?

We aimed to characterize the cerebral hemodynamic response to obstructive sleep apnea/hypopnea events, and evaluate their association to polysomnographic parameters. The characterization of the cerebral hemodynamics in obstructive sleep apnea (OSA) may add complementary information to further the understanding of the severity of the syndrome beyond the conventional polysomnography. Severe OSA patients were studied during night sleep while monitored by polysomnography. Transcranial, bed-side diffuse correlation spectroscopy (DCS) and frequency-domain near-infrared diffuse correlation spectroscopy (NIRS-DOS) were used to follow microvascular cerebral hemodynamics in the frontal lobes of the cerebral cortex. Changes in cerebral blood flow (CBF), total hemoglobin concentration (THC), and cerebral blood oxygen saturation (StO2) were analyzed. We considered 3283 obstructive apnea/hypopnea events from sixteen OSA patients (Age (median, interquartile range) 57 (52-64.5); females 25%; AHI (apnea-hypopnea index) 84.4 (76.1-93.7)). A biphasic response (maximum/minimum followed by a minimum/maximum) was observed for each cerebral hemodynamic variable (CBF, THC, StO2), heart rate and peripheral arterial oxygen saturation (SpO2). Changes of the StO2 followed the dynamics of the SpO2, and were out of phase from the THC and CBF. Longer events were associated with larger CBF changes, faster responses and slower recoveries. Moreover, the extrema of the response to obstructive hypopneas were lower compared to apneas (p < .001). Obstructive apneas/hypopneas cause profound, periodic changes in cerebral hemodynamics, including periods of hyper- and hypo-perfusion and intermittent cerebral hypoxia. The duration of the events is a strong determinant of the cerebral hemodynamic response, which is more pronounced in apnea than hypopnea events.

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

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

Microvascular blood flow changes of the abductor pollicis brevis muscle during sustained static exercise.

A practical assessment of the general health and microvascular function of the palm muscle, abductor pollicis brevis (APB), is important for the diagnosis of different conditions. In this study, we have developed a protocol and a probe to study microvascular blood flow using near-infrared diffuse correlation spectroscopy (DCS) in APB during and after thumb abduction at 55% of maximum voluntary contraction (MVC). Near-infrared time resolved spectroscopy (TRS) was also used to characterize the baseline optical and hemodynamic properties. Thirteen (n=13) subjects were enrolled and subdivided in low MVC (N=6, MVC<2.3 kg) and high MVC (N=7, MVC≥2.3 kg) groups. After ruling out significant changes in the systemic physiology that influence the muscle hemodynamics, we have observed that the high MVC group showed a 56% and 36% decrease in the blood flow during exercise, with respect to baseline, in the long and short source-detector (SD) separations (p=0.031 for both). No statistical differences were shown for the low MVC group (p=1 for short and p=0.15 for long SD). These results suggest that the mechanical occlusion, due to increased intramuscular pressure, exceeded the vasodilation elicited by the higher metabolic demand. Also, blood flow changes during thumb contraction negatively correlated (R=-0.7, p<0.01) with the absolute force applied by each subject. Furthermore, after the exercise, muscular blood flow increased significantly immediately after thumb contractions in both high and low MVC groups, with respect to the recorded values during the exercise (p=0.031). An increase of 251% (200%) was found for the long (short) SD in the low MVC group. The high MVC groups showed a significant 90% increase in blood flow only after 80 s from the start of the protocol. For both low and high MVC groups, blood flow recovered to baseline values within 160 s from starting the exercise. In conclusion, DCS allows the study of the response of a small muscle to static exercise and can be potentially used in multiple clinical conditions scenarios for assessing microvascular health.

Impact of changes in tissue optical properties on near-infrared diffuse correlation spectroscopy measures of skeletal muscle blood flow.

Near-infrared diffuse correlation spectroscopy (DCS) is increasingly used to study relative changes in skeletal muscle blood flow. However, most diffuse correlation spectrometers assume that tissue optical properties-such as absorption (μa) and reduced scattering (μ's) coefficients-remain constant during physiological provocations, which is untrue for skeletal muscle. Here, we interrogate how changes in tissue μa and μ's affect DCS calculations of blood flow index (BFI). We recalculated BFI using raw autocorrelation curves and μa/μ's values recorded during a reactive hyperemia protocol in 16 healthy young individuals. First, we show that incorrectly assuming baseline μa and μ's substantially affects peak BFI and BFI slope when expressed in absolute terms (cm2/s, P < 0.01), but these differences are abolished when expressed in relative terms (% baseline). Next, to evaluate the impact of physiologic changes in μa and μ's, we compared peak BFI and BFI slope when μa and μ's were held constant throughout the reactive hyperemia protocol versus integrated from a 3-s rolling average. Regardless of approach, group means for peak BFI and BFI slope did not differ. Group means for peak BFI and BFI slope were also similar following ad absurdum analyses, where we simulated supraphysiologic changes in μa/μ's. In both cases, however, we identified individual cases where peak BFI and BFI slope were indeed affected, with this result being driven by relative changes in μa over μ's. Overall, these results provide support for past reports in which μa/μ's were held constant but also advocate for real-time incorporation of μa and μ's moving forward.NEW & NOTEWORTHY We investigated how changes in tissue optical properties affect near-infrared diffuse correlation spectroscopy (NIR-DCS)-derived indices of skeletal muscle blood flow (BFI) during physiological provocation. Although accounting for changes in tissue optical properties has little impact on BFI on a group level, individual BFI calculations are indeed impacted by changes in tissue optical properties. NIR-DCS calculations of BFI should therefore account for real-time, physiologically induced changes in tissue optical properties whenever possible.

Kinetic differences between macro- and microvascular measures of reactive hyperemia.

Postischemia reperfusion kinetics are markedly dissociated when comparing the macro- versus microvasculature. We used Doppler ultrasound and near-infrared diffuse correlation spectroscopy (NIR-DCS), an emerging technique for continuously and noninvasively quantifying relative changes in skeletal muscle microvascular perfusion (i.e., blood flow index or BFI), to measure macro- and microvascular reactive hyperemia (RH) in the nondominant arm of 16 healthy young adults. First, we manipulated the duration of limb ischemia (3 vs. 6 min) with the limb at heart level (neutral, -N). Then, we reduced/increased forearm perfusion pressure (PP) by positioning the arm above (3 min-A, 60°) or below (3 min-B, 30°) the heart. The major novel findings were twofold: first, changes in the ischemic stimulus similarly affected peak macrovascular (i.e., conduit, mL/min) and microvascular (i.e., peak NIR-DCS-derived BFI) reperfusion during reactive hyperemia (6 min-N > 3 min-N, P < 0.05, both) but did not affect the rate at which microvascular reperfusion occurs (i.e., BFI slope). Second, changing forearm PP predictably affected both peak macro- and microvascular reperfusion during RH (3 min-B > N > A, P < 0.05, all), as well as the rate at which microvascular reperfusion occurred (BFI slope; 3 min-B >N > A, P < 0.05). Together, the data suggest that kinetic differences between macro- and microvascular reperfusion are largely determined by differences in fluid mechanical energy (i.e., pressure, gravitational, and kinetic energies) between the two compartments that work in tandem to restore pressure across the arterial tree following a period of tissue ischemia.NEW & NOTEWORTHY We extend our understanding of macro- versus microvascular hemodynamics in humans, by using near-infrared diffuse correlation spectroscopy (micro-) and Doppler ultrasound (macro-) to characterize reperfusion hemodynamics following experimental manipulation of the ischemic stimulus and tissue perfusion pressure. Our results suggest kinetic differences between macro- and microvascular reperfusion are largely determined by differences in fluid mechanical energy (i.e., pressure, gravitational, and kinetic energies) between the two compartments, rather than inherent differences between the macro- and microvasculature.

Evaluation Of Functional Sympatholysis Occurring Within Contracting Skeletal Muscle Microvasculature In Humans

The ability of contracting skeletal muscle to blunt sympathetic vasoconstriction, termed functional sympatholysis, is thought to contribute to supplying adequate blood to the exercising muscle despite increased sympathetic tone. However, previous studies in humans primarily investigated vascular responses of exercising limb as a whole that reflects not only responses of contracting skeletal muscles but also responses of inactive tissues such as skin, adipose and bones. PURPOSE: We aimed to more directly investigate the functional sympatholysis occurring within exercising skeletal muscle in humans. METHODS: In 26 healthy male volunteers, we examined the effects of acute sympathoexcitation by 90-s forehead cooling at rest and during dynamic handgrip exercise at 10% and 30% of maximum voluntary contraction (10%Ex and 30%Ex), respectively. The handgrip exercises were continued 3 min and forehead cooling was applied at latter half of the exercise period. The subjects also performed handgrip exercises without forehead cooling as control conditions. We employed near-infrared diffuse correlation spectroscopy, an emerging optical technique for noninvasive measurement of deep tissue hemodynamics, to continuously measure the microcirculatory blood flow index (BFI) within the flexor digitorum superficialis muscle, the muscle primarily responsible for handgrip. RESULTS: The acute sympathoexcitation induced significant decrease in vascular conductance (BFI / mean arterial pressure) at rest (baseline vs. forehead cooling: 1.00 ± 0 vs. 0.75 ± 0.03 AU, p < 0.05) and during 10%Ex (control vs. forehead cooling: 1.66 ± 0.08 vs. 1.32 ± 0.10 AU, p < 0.05), but not during 30%Ex (control vs. forehead cooling: 4.00 ± 0.56 vs. 3.66 ± 0.50 AU, p > 0.05). In addition, the percentage reduction in vascular conductance by forehead cooling was significantly decreased during 30%Ex compared to rest (-25.2 ± 2.5 vs. -4.9 ± 5.1 %, p < 0.05). CONCLUSIONS: Our study demonstrated the functional sympatholysis occurring within the contracting skeletal muscle microvasculature in humans. Furthermore, our results revealed the clear intensity-dependent response such that mild exercise hardly interferes with sympathetic vasoconstriction, whereas moderate exercise substantially attenuates it.

MON-488 Technologies of Diffuse Optics in the Diagnosis of Thyroid Cancer

BACKGROUND:The most common tool to test malignancy in the study of thyroid nodules (NT) is ultrasound and fine needle aspiration biopsy (FNAB). However, the sensitivity and specificity of the method and the effectiveness in thyroid cancer are limited; therefore new methods to study thyroid nodules are required. In this way our goal is to introduce hybrid diffuse optical instruments that are capable to measure and discriminate altered microvascular blood flow, blood volume and tissue scattering coefficients of TN. Near-infrared diffuse optical technologies aim to overcome the shortcomings of present techniques while screening for malignant thyroid nodules for early and fast diagnosis of cancer. This idea was based on the previous experience in breast cancers with diffuse optical techniques.METHODS:We have developed a device based on near-infrared diffuse correlation spectroscopy (DCS), which is a technology aimed at retrieving the microvascular flow of a certain region of tissue by mean of low power near-infrared laser light, and used in combination with a commercial ultrasound system (US). In order to combine these devices, we have developed a probe enabling multimodal data acquisition and subsequently we have analyzed the optical properties and the blood flow index in the thyroid lobes of eleven subjects who presented a thyroid nodule.RESULTS:Four subjects have required FNAB: P4 and P7 were reported as being malignant (Bethesda VI and IV respectively) while P6 and P8 were evaluated as being benign (Bethesda II). Surgical removal confirmed papillary thyroid carcinoma in P4, while denied the result of FNAB for P7 (Multinodular thyroid hyperplasia). We have considered the contralateral lobe as intra-subject reference to validate the feasibility of the DCS system in a very absorbing tissue as thyroid is. The difference between the blood flow index of the nodule and the contralateral lobe is maximum for subject P4, while the difference in benign subjects is lower. T-test showed no significant difference between benign nodules and contralateral lobes. Subject P7 showed a small difference as for other benign subjects despite the FNAB results indicating presence of malignancy.CONCLUSION:Apparently diffuse optics technologies would be able to differentiate malignant thyroid nodules from benign thyroid nodules, but more measurements require confirming our preliminary results as that diffuse optical technology can complement the current techniques such as US and FNAB.A new measurement campaign is being scheduled with a completed, fully integrated device that was developed within the LUCA project (http://www.luca-project.eu).

Diffuse correlation spectroscopy and frequency-domain near-infrared spectroscopy for measuring microvascular blood flow in dynamically exercising human muscles

In the last 20 yr, near-infrared diffuse correlation spectroscopy (DCS) has been developed for providing a noninvasive estimate of microvascular blood flow (BF) as a BF index (BFi) in the human skin, muscle, breast, brain, and other tissue types. In this study, we proposed a new motion correction algorithm for DCS-derived BFi able to remove motion artifacts during cycling exercise. We tested this algorithm on DCS data collected during cycling exercise and demonstrated that DCS can be used to quantify muscle BFi during dynamic high-intensity exercise. In addition, we measured tissue regional oxygen metabolic rate (MRO2i) by combining frequency-domain multidistance near-infrared spectroscopy (FDNIRS) oximetry with DCS flow measures. Recreationally active subjects (n = 12; 31 ± 8 yr, 183 ± 4 cm, 79 ± 10 kg) pedaled at 80-100 revolutions/min until volitional fatigue with a work rate increase of 30 W every 4 min. Exercise intensity was normalized in each subject to the cycling power peak (Wpeak). Both rectus femoris BFi and MRO2i increased from 15% up to 75% Wpeak and then plateaued to the end of the exercise. During the recovery at 30 W cycling power, BFi remained almost constant, whereas MRO2i started to decrease. The BFi/MRO2i plateau was associated with the rising of the lactate concentration, indicating the progressive involvement of the anaerobic metabolism. These findings further highlight the utility of DCS and FDNIRS oximetry as effective, reproducible, and noninvasive techniques to assess muscle BFi and MRO2i in real time during a dynamic exercise such as cycling.NEW & NOTEWORTHY To the best of our knowledge, this study is the first to demonstrate that diffuse correlation spectroscopy in combination with frequency-domain near-infrared spectroscopy can monitor human quadriceps microvascular blood flow and oxygen metabolism with high temporal resolution during a cycling exercise. The optically measured parameters confirm the expected relationship between blood flow, muscle oxidative metabolism, and lactate production during exercise.

Studies into the determinants of skeletal muscle oxygen consumption: novel insight from near-infrared diffuse correlation spectroscopy.

Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion. Near-infrared spectroscopy (NIRS) is an established technique for characterizing the transport and utilization of oxygen through the microcirculation. Here we compared a combined NIRS-DCS system with conventional measures of oxygen delivery and utilization during handgrip exercise. The data show good concurrent validity between convective oxygen delivery and DCS-derived blood flow index, as well as between oxygen extraction at the conduit and microvascular level. We then manipulated forearm arterial perfusion pressure by adjusting the position of the exercising arm relative to the position of the heart. The data show that microvascular perfusion can be uncoupled from convective oxygen delivery, and that tissue saturation seemingly compensates to maintain skeletal muscle oxygen consumption. Taken together, these data support a novel role for NIRS-DCS in understanding the determinants of muscle oxygen consumption at the microvascular level. Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion. Combining DCS with near-infrared spectroscopy (NIRS) introduces exciting possibilities for understanding the determinants of muscle oxygen consumption; however, no investigation has directly compared NIRS-DCS to conventional measures of oxygen delivery and utilization in an exercising limb. To address this knowledge gap, nine healthy males performed rhythmic handgrip exercise with simultaneous measurements by NIRS-DCS, Doppler blood flow and venous oxygen content. The two approaches showed good concurrent validity, with directionally similar responses between: (a) Doppler-derived forearm blood flow and DCS-derived blood flow index (BFI), and (b) venous oxygen saturation and NIRS-derived tissue saturation. To explore the utility of combined NIRS-DCS across the physiological spectrum, we manipulated forearm arterial perfusion pressure by altering the arm position above or below the level of the heart. As expected, Doppler-derived skeletal muscle blood flow increased with exercise in both arm positions, but with markedly different magnitudes (below: +424.3±41.4ml/min, above: +306±12.0ml/min, P=0.002). In contrast, DCS-derived microvascular BFI increased to a similar extent with exercise, regardless of arm position (P=0.65). Importantly, however, the time to reach BFI steady state was markedly slower with the arm above the heart, supporting the experimental design. Notably, we observed faster tissue desaturation at the onset of exercise with the arm above the heart, resulting in similar muscle oxygen consumption profiles throughout exercise. Taken together, these data support a novel role for NIRS-DCS in understanding the determinants of skeletal muscle oxygen utilization non-invasively and throughout exercise.

Local In Vivo Measures of Muscle Lipid and Oxygen Consumption Change in Response to Combined Vitamin D Repletion and Aerobic Training in Older Adults.

Intramyocellular (IMCL), extramyocellular lipid (EMCL), and vitamin D deficiency are associated with muscle metabolic dysfunction. This study compared the change in [IMCL]:[EMCL] following the combined treatment of vitamin D and aerobic training (DAT) compared with vitamin D (D), aerobic training (AT), and control (CTL). Male and female subjects aged 60–80 years with a BMI ranging from 18.5–34.9 and vitamin D status of ≤32 ng/mL (25(OH)D) were recruited to randomized, prospective clinical trial double-blinded for supplement with a 2 × 2 factorial design. Cholecalciferol (Vitamin D3) (10,000 IU × 5 days/week) or placebo was provided for 13 weeks and treadmill aerobic training during week 13. Gastrocnemius IMCL and EMCL were measured with magnetic resonance spectroscopy (MRS) and MRI. Hybrid near-infrared diffuse correlation spectroscopy measured hemodynamics. Group differences in IMCL were observed when controlling for baseline IMCL (p = 0.049). DAT was the only group to reduce IMCL from baseline, while a mean increase was observed in all other groups combined (p = 0.008). IMCL reduction and the corresponding increase in rVO2 at study end (p = 0.011) were unique to DAT. Vitamin D, when combined with exercise, may potentiate the metabolic benefits of exercise by reducing IMCL and increasing tissue-level VO2 in healthy, older adults.

Microvascular cerebral blood flow fluctuations in association with apneas and hypopneas in acute ischemic stroke.

In a pilot study on acute ischemic stroke (AIS) patients, unexpected periodic fluctuations in microvascular cerebral blood flow (CBF) had been observed. Motivated by the relative lack of information about the impact of the emergence of breathing disorders in association with stroke on cerebral hemodynamics, we hypothesized that these fluctuations are due to apneic and hypopneic events. A total of 28 patients were screened within the first week after stroke with a pulse oximeter. Five (18%) showed fluctuations of arterial blood oxygen saturation ( ) and were included in the study. Near-infrared diffuse correlation spectroscopy (DCS) was utilized bilaterally to measure the frontal lobe CBF alongside respiratory polygraphy. Biphasic CBF fluctuations were observed with a bilateral increase of and for the ipsilesional and contralesional hemispheres, respectively, and a decrease of and for the ipsilesional and contralesional hemispheres, respectively. The polygraph revealed that, in general, the fluctuations were associated with apneic and hypopneic events. This study motivates us to investigate whether the impact of altered respiratory patterns on cerebral hemodynamics can be detrimental in AIS patients.

Partitioning key determinants of oxygen consumption: Novel insight from Dual Wavelength Diffuse Correlation Spectroscopy

Near‐infrared diffuse correlation spectroscopy (DCS) is an emerging technique for non‐invasive measurement of local muscle blood flow at the microvascular level. We have previously shown excellent agreement between single wavelength DCS and Doppler ultrasound of the brachial artery during rhythmic handgrip exercise, supporting the role of DCS in exercise physiology. Here, we report novel DCS data from our lab, incorporating two‐different wavelengths (785 nm and 852 nm), allowing for direct assessment of microvascular perfusion, together with oxyhemoglobin and deoxyhemoglobin. To‐date, we have studied eight individuals (male/female: 3/5, mean: age 48±22 (range: 22–76 years), height 170±8 cm, and weight 75±12 kg). Subjects were instrumented with the DCS probe located over the belly of the flexor digitorum profundus. Duplex ultrasound of the brachial artery was also performed as a secondary measure of skeletal muscle blood flow. Each subject performed two bouts of rhythmic hand grip exercise at 20% of their maximum voluntary contraction (MVC). Each exercise bout was preceded by a standardized resting baseline, and each period of data collection was separated by at least 10 minutes of rest. Data from each round of data collection were averaged. As reported previously using our single wavelength DCS device, blood flow index (BFI, the primary output from DCS) increased significantly (119±37%) with exercise. We also observed a −1.9±1.1% change in oxyhemoglobin and 21.8±10.0% change in deoxyhemoglobin resulting in a −5.9±2.6% change in tissue saturation with exercise. As a result, relative muscle oxygen consumption (rmVO2) increased by 160.2±55.4%. The novelty of this new approach is best illustrated by a case‐comparison between two subjects, who performed similar absolute (11 vs 10 kg) and relative work (20%), and yet achieved disparate levels of oxygen utilization during exercise (ΔrmO2 = 307% vs. 214%, Case A vs. Case B respectively). This difference appears to be explained predominantly by muscle oxygen extraction as both brachial artery blood flow and microvascular perfusion (by DCS) were similar in both subjects. In contrast, Case A exhibited a much greater change in StO2 (−17.8%) compared to Case B, whose StO2 more closely mirrored the group average (−6.8%). To help interpret these results, we evaluated skeletal muscle oxidative capacity in both subjects using an established NIRS‐based cuff occlusion protocol (Rosenberry et al. 2018. JoVE). Remarkably, these additional data corroborated our assumptions, showing a muscle oxygen consumption recovery time of 34 seconds in Case A and 93 seconds in Case B. Taken together, these data establish strong proof‐of‐concept that dual wavelength DCS can provide important mechanistic insight into the determinants of oxygen consumption. Extending these findings to patients with exercise intolerance (e.g. heart failure with preserved or reduced ejection fraction) may provide important therapeutic insight.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Principles, insights, and potential pitfalls of the noninvasive determination of muscle oxidative capacity by near-infrared spectroscopy.

Skeletal muscle oxidative capacity is highly plastic, strongly associated with whole-body aerobic capacity (16, 18) and state of health. Loss of muscle oxidative capacity is associated with physical inactivity, aging and chronic disease (17), and has been implicated in the pathophysiology of obesity and diabetes (21). Evaluating these changes has traditionally been limited to invasive or costly assessments (biopsy or ³¹P MRS). To address this, Hamaoka and colleagues developed an innovative, non-invasive approach using near-infrared spectroscopy (NIRS) to quantitatively measure muscle oxygen consumption (mVO₂; 12) and use this to infer muscle oxidative capacity based on the mVO₂ recovery rate constant (k) (23; later modified 26). This technique has been subsequently used to interpret relative differences in oxidative capacity across a wide range of muscles, ages and disease states (Figure 1C). The purpose of this Viewpoint is to open a discussion on the principles, insights and potential pitfalls of using NIRS to measure k and infer muscle oxidative capacity.

Measurement of Skeletal Muscle Blood Flow with Near‐infrared Diffuse Correlation Spectroscopy

Direct continuous noninvasive measurement of local muscle blood flow in humans remains limited. Conventional measurements of limb blood flow, such as Doppler ultrasound or venous occlusion plethysmography, measure changes in bulk conduit flow and do not provide regional information. Near‐infrared diffuse correlation spectroscopy (DCS) is an emerging technique for non‐invasive measurement of local muscle blood flow at the microvascular level. In order to better understand the strengths and limitations of this novel approach, we performed a validation study by comparing muscle blood flow changes measured by DCS and Doppler ultrasound during exercise. Ten subjects were recruited for this study (age: 27±3 yrs; female/male: 1/9; BMI: 27.0±3.6 kg/m2). The DCS probe was affixed to the forearm over the belly of the flexor digitorum profundus. Brachial artery blood velocity and diameter were measured with Doppler ultrasound, integrated, and reported as brachial artery blood flow. After a brief period of rest, each participant performed rhythmic handgrip exercise at 20% and 50% of their maximum voluntary contraction (MVC). As expected, brachial artery blood flow increased significantly from baseline by 312±56% at 20% MVC, and 613±90% at 50% MVC. Blood flow index (BFI), the primary output from DCS, shared a similar change from baseline, increasing 112±18% and 262±35%, respectively. To more appropriately compare these two approaches, the data were normalized to each person's individual maximum for each respective technique. Remarkably, the increase in skeletal muscle blood flow was strikingly similar between the two techniques, when reported in normalized units (20%: 0.42±0.03 vs. 0.45±0.03; 50%: 0.69±0.04 vs. 0.79±0.02, DCS vs. BA flow, respectively). The change in skeletal muscle blood flow by DCS and Doppler ultrasound were also strongly correlated (r2=0.77, P&lt;0.001). Taken together, these data show that DCS and Doppler ultrasound quantify the same temporal dynamics of skeletal muscle blood flow during exercise. While these results are indeed encouraging, more work is needed to fully validate this approach for measuring local microvascular blood flow in humans.Support or Funding InformationThis work was support by an Interdisciplinary Research Program grant from the University of Texas at Arlington.

Obstructive sleep apnea–hypopnea results in significant variations in cerebral hemodynamics detected by diffuse optical spectroscopies

The objective of this study was to adapt a novel near-infrared diffuse correlation spectroscopy (DCS) flow-oximeter for simultaneous and continuous monitoring of relative changes in cerebral blood flow (rCBF) and cerebral oxygenation (i.e. oxygenated/deoxygenated/total hemoglobin concentration: Δ[HbO2]/Δ[Hb]/ΔTHC) during overnight nocturnal polysomnography (NPSG) diagnostic test for obstructive sleep apnea–hypopnea (OSAH). A fiber-optic probe was fixed on subject’s frontal head and connected to the DCS flow-oximeter through a custom-designed fiber-optic connector, which allowed us to easily connect/detach the optical probe from the device when the subject went to bathroom. To minimize the disturbance to the subject, the DCS flow-oximeter was remotely operated by a desktop located in the control room. The results showed that apneic events caused significant variations in rCBF and ΔTHC. Moreover, the degrees of variations in all measured cerebral variables were significantly correlated with the severity of OSAH as determined by the apnea–hypopnea index (AHI), demonstrating the OSAH influence on both CBF and cerebral oxygenation. Large variations in arterial blood oxygen saturation (SaO2) were also found during OSAH. Since frequent variations/disturbances in cerebral hemodynamics may adversely impact brain function, future study will investigate the correlations between these cerebral variations and functional impairments for better understanding of OSAH pathophysiology.

Shear-Sensitive Regulation of Neutrophil Flow Behavior and Its Potential Impact on Microvascular Blood Flow Dysregulation in Hypercholesterolemia

Shear stress-induced pseudopod retraction is an anti-inflammatory measure that minimizes neutrophil activity and is regulated by membrane cholesterol. We tested the hypothesis that a hypercholesterolemic impairment of shear mechanotransduction alters the neutrophil flow behavior leading to microvascular dysfunction. We examined the shear effects on the flow behavior of human leukocytes. When subjected to shearing during cone-plate viscometry, leukocyte suspensions exhibited parallel time-dependent reductions in viscosity and pseudopod activity. Shear-induced reductions in suspension viscosity were attenuated by membrane cholesterol enrichment. We also showed that enhanced pseudopod activity of leukocyte suspensions in 10% hematocrit significantly (P<0.05) raised the flow resistance of microvascular mimics. These results implicate an impaired neutrophil pseudopod retraction response to shear in hypercholesterolemic microvascular dysfunction. We confirmed this using near-infrared diffuse correlation spectroscopy to assess skeletal muscle blood flow regulation in the hindlimbs of mice subjected to reactive hyperemia. Using a custom protocol for the mouse, we extrapolated an adjusted peak flow and time to adjusted peak flow to quantify the early phase of the blood flow recovery response during reactive hyperemia when shear mechanobiology likely has a maximal impact. Compared with mice on normal diet, hypercholesterolemic mice exhibited significantly (P<0.05) reduced adjusted peak flow and prolonged time to adjusted peak flow which correlated (r=0.4 and r=-0.3, respectively) with neutrophil shear responsiveness and were abrogated by neutropenia. These results provide the first evidence that the neutrophils contribute to tissue blood flow autoregulation. Moreover, a deficit in the neutrophil responsiveness to shear may be a feature of hypercholesterolemia-related microvascular dysfunction.

Noninvasive quantification of postocclusive reactive hyperemia in mouse thigh muscle by near-infrared diffuse correlation spectroscopy

Many vasculature-related diseases affecting skeletal muscle function have been studied in mouse models. Noninvasive quantification of muscle blood flow responses during postocclusive reactive hyperemia (PORH) is often used to evaluate vascular function in human skeletal muscles. However, blood flow measurements during PORH in small skeletal muscles of mice are rare due to the lack of appropriate technologies coupled with the challenge of measurement setup resulting from the lack of large enough test sites. In this study, we explored adapting diffuse correlation spectroscopy (DCS) for noninvasive measurement of the relative changes of blood flow (rBF) in mouse thigh muscles during PORH. A small fiber-optic probe was designed and glued on the mouse thigh to reduce the motion artifact induced by the occlusion procedure. Arterial occlusion was created by tying a polyvinyl chloride (PVC) tube around the mouse thigh while the muscle rBF was continuously monitored by DCS to ensure the success of the occlusion. After 5 min, the occlusion was rapidly released by severing the PVC tube using a cautery pen. Typical rBF responses during PORH were observed in all mice (n=7), which are consistent with those observed by arterial-spin-labeled magnetic resonance imaging (ASL-MRI) as reported in the literature. On average, rBF values from DCS during occlusion were lower than 10% (3.1±2.2%) of the baseline values (assigning 100%), indicating the success of arterial occlusion in all mice. Peak values of rBF during PORH measured by the DCS (357.6±36.3%) and ASL-MRI (387.5±150.0%) were also similar whereas the values of time-to-peak (the time duration from the end of occlusion to the peak rBF) were quite different (112.6±35.0 s versus 48.0±27.0 s). Simultaneous measurements by these two techniques are needed to identify the factors that may cause such discrepancy. This study highlights the utility of DCS technology to quantitatively evaluate tissue blood flow responses during PORH in mouse skeletal muscles. DCS holds promise as valuable tool to assess blood flow regulation in mouse models with a variety of vascular diseases (e.g., hypercholesterolemia, diabetes, peripheral artery disease).

Application of near infrared diffuse correlation spectroscopy in noninvasive monitoring of tumor photodynamic therapy

A novel near-infrared (NIR) diffuse correlation spectroscopy (DCS) has recently been developed for noninvasive monitoring of tumor blood flow during photodynamic therapy (PDT).DCS offers several attractive new features for tumor blood flow measurement such as noninvasiveness,portability,low cost,high temporal resolution and relatively large penetration depth.DCS technology has been utilized for continuous measurement of tumor blood flow before,during and after PDT in both animals and humans.The ultimate goal is to predict treatment outcomes from the measured tumor hemodynamic responses to PDT. Key words: Diffusion; Correlation; Spectroscopy; Blood flow; Cancer; Photodynamic therapy

Diffuse Correlation Spectroscopy (DCS) for Assessment of Tissue Blood Flow in Skeletal Muscle: Recent Progress.

Near-infrared diffuse correlation spectroscopy (DCS) is an emerging technology for monitoring blood flow in various tissues. This article reviews the recent progress of DCS for the assessment of skeletal muscle blood flow, including the developments in technology allowing use during dynamic exercise and muscular electrical stimulation, the utilization for diagnosis of muscle vascular diseases, and the applications for evaluating treatment effects. The limitations of current DCS studies and future perspective are finally discussed.

Simultaneously Extracting Multiple Parameters via Fitting One Single Autocorrelation Function Curve in Diffuse Correlation Spectroscopy

Near-infrared diffuse correlation spectroscopy (DCS) has recently been employed for noninvasive acquisition of blood flow information in deep tissues. Based on the established correlation diffusion equation, the light intensity autocorrelation function detected by DCS is determined by a blood flow index αD(B), tissue absorption coefficient μ(a), reduced scattering coefficient μ'(s), and a coherence factor β. This study is designed to investigate the possibility of extracting multiple parameters such as μ(a), μ'(s), β, and αD(B) through fitting one single autocorrelation function curve and evaluate the performance of different fitting methods. For this purpose, computer simulations, tissue-like phantom experiments, and in vivo tissue measurements were utilized. The results suggest that it is impractical to simultaneously fit αD(B) and μ(a) or αD(B) and μ'(s) from one single autocorrelation function curve due to the large crosstalk between these paired parameters. However, simultaneously fitting β and αD(B) is feasible and generates more accurate estimation with smaller standard deviation compared to the conventional two-step fitting method (i.e., first calculating β and then fitting αD(B)). The outcomes from this study provide a crucial guidance for DCS data analysis.