non-invasive-monitoring-microvascular-oxygenation-reactive-hyperemia

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no ...

Hemophotonics s.l.

The in vivo optical and hemodynamic properties of the healthy (n = 22) and pathological (n = 2) human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs') at three wavelengths (690, 785 and 830 nm) to derive total hemoglobin concentration (THC) and oxygen saturation (StO2). DCS measured the microvascular blood flow index (BFI). Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s) compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s), while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%), yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies.

We present the recipe and characterization for preparing liquid phantoms that are suitable for both near-infrared spectroscopy and diffuse correlation spectroscopy. The phantoms have well-defined and tunable optical and dynamic properties, and consist of a solution of water and glycerol with fat emulsion as the scattering element. The recipe takes into account the effect of bulk refractive index changes due to the addition of glycerol, which is commonly used to alter the sample viscosity.

Liquid phantoms for near-infrared and diffuse correlation spectroscopies with tunable optical and dynamic properties.

A new device that combines, for the first time, two photonic technologies (time-resolved near-infrared spectroscopy and diffuse correlation spectroscopy) was provided and tested within the BabyLux project. Aim was to validate the expected changes in cerebral oxygenation and blood flow.

Cerebral oxygenation and blood flow in term infants during postnatal transition: BabyLux project.

The BabyLux device is a hybrid diffuse optical neuromonitor that has been developed and built to be employed in neonatal intensive care unit for the noninvasive, cot-side monitoring of microvascular cerebral blood flow and blood oxygenation. It integrates time-resolved near-infrared and diffuse correlation spectroscopies in a user-friendly device as a prototype for a future medical grade device. We present a thorough characterization of the device performance using test measurements in laboratory settings. Tests on solid phantoms report an accuracy of optical property estimation of about 10%, which is expected when using the photon diffusion equation as the model. The measurement of the optical and dynamic properties is stable during several hours of measurements within 3% of the average value. In addition, these measurements are repeatable between different days of measurement, showing a maximal variation of 5% in the optical properties and 8% for the particle diffusion coefficient on a liquid phantom. The variability over test/retest evaluation is  . The integration of the two modalities is robust and without any cross talk between the two. We also perform  measurements on the adult forearm during arterial cuff occlusion to show that the device can measure a wide range of tissue hemodynamic parameters. We suggest that this platform can form the basis of the next-generation neonatal neuromonitors to be developed for extensive, multicenter clinical testing.

BabyLux device: a diffuse optical system integrating diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy for the neuromonitoring of the premature newborn brain.

We have investigated the accuracy and precision of "the BabyLux device", a hybrid time-resolved near-infrared (TRS) and diffuse correlation spectroscopy (DCS) neuro-monitor for the pre-term infant. Numerical data with realistic noise were simulated and analyzed using the BabyLux device as a reference system and different experimental and analysis parameters. The results describe the limits for the precision and the accuracy to be expected. The dependence of these limits on different experimental conditions and choices of the analysis method is also described. Experiments demonstrate comparable values for precision with respect to the simulation results.

Accuracy and precision of tissue optical properties and hemodynamic parameters estimated by the BabyLux device: a hybrid time-resolved near-infrared and diffuse correlation spectroscopy neuro-monitor.

Diffuse correlation spectroscopy (DCS) can non-invasively and continuously asses regional cerebral blood flow (rCBF) at the cot-side by measuring a blood flow index (BFI) in non-traditional units of cm/s. We have validated DCS against positron emission tomography using O-labeled water (O-water PET) in a piglet model allowing us to derive a conversion formula for BFI to rCBF in conventional units (ml/100g/min). Neonatal piglets were continuously monitored by the BabyLux device integrating DCS and time resolved near infrared spectroscopy (TRS) while acquiring O-water PET scans at baseline, after injection of acetazolamide and during induced hypoxic episodes. BFI by DCS was highly correlated with rCBF (R = 0.94,  < 0.001) by PET. A scaling factor of 0.89 (limits of agreement for individual measurement: 0.56, 1.39)×10× (ml/100g/min)/(cm/s) was used to derive baseline rCBF from baseline BFI measurements of another group of piglets and of healthy newborn infants showing an agreement with expected values. These results pave the way towards non-invasive, cot-side absolute CBF measurements by DCS on neonates.

Validation of diffuse correlation spectroscopy against O-water PET for regional cerebral blood flow measurement in neonatal piglets.

Intracranial pressure (ICP) is an important parameter to monitor in several neuropathologies. However, because current clinically accepted methods are invasive, its monitoring is limited to patients in critical conditions. On the other hand, there are other less critical conditions for which ICP monitoring could still be useful; therefore, there is a need to develop non-invasive methods. We propose a new method to estimate ICP based on the analysis of the non-invasive measurement of pulsatile, microvascular cerebral blood flow with diffuse correlation spectroscopy. This is achieved by training a recurrent neural network using only the cerebral blood flow as the input. The method is validated using a 50% split sample method using the data from a proof-of-concept study. The study involved a population of infants ( = 6) with external hydrocephalus (initially diagnosed as benign enlargement of subarachnoid spaces) as well as a population of adults ( = 6) with traumatic brain injury. The algorithm was applied to each cohort individually to obtain a model and an ICP estimate. In both diverse cohorts, the non-invasive estimation of ICP was achieved with an accuracy of <4 mm Hg and a negligible small bias. Further, we have achieved a good correlation (Pearson's correlation coefficient >0.9) and good concordance (Lin's concordance correlation coefficient >0.9) in comparison with standard clinical, invasive ICP monitoring. This preliminary work paves the way for further investigations of this tool for the non-invasive, bedside assessment of ICP.

Non-Invasive Estimation of Intracranial Pressure by Diffuse Optics: A Proof-of-Concept Study.

Over the recent years, a typical implementation of diffuse correlation spectroscopy (DCS) instrumentation has been adapted widely. However, there are no detailed and accepted recipes for designing such instrumentation to meet pre-defined signal-to-noise ratio (SNR) and precision targets. These require specific attention due to the subtleties of the DCS signals. Here, DCS experiments have been performed using liquid tissue simulating phantoms to study the effect of the detected photon count-rate, the number of parallel detection channels and the measurement duration on the precision and SNR to suggest scaling relations to be utilized for device design.

Recipes for diffuse correlation spectroscopy instrument design using commonly utilized hardware based on targets for signal-to-noise ratio and precision.

We present the LUCA device, a multi-modal platform combining eight-wavelength near infrared time resolved spectroscopy, sixteen-channel diffuse correlation spectroscopy and a clinical ultrasound in a single device. By simultaneously measuring the tissue hemodynamics and performing ultrasound imaging, this platform aims to tackle the low specificity and sensitivity of the current thyroid cancer diagnosis techniques, improving the screening of thyroid nodules. Here, we show a detailed description of the device, components and modules. Furthermore, we show the device tests performed through well established protocols for phantom validation, and the performance assessment for . The characterization tests demonstrate that LUCA device is capable of performing high quality measurements, with a precision in determining  tissue optical and dynamic properties of better than 3%, and a reproducibility of better than 10% after ultrasound-guided probe repositioning, even with low photon count-rates, making it suitable for a wide variety of clinical applications.

The LUCA device: a multi-modal platform combining diffuse optics and ultrasound imaging for thyroid cancer screening.

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.

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

The optical measurement of cerebral oxygen metabolism was evaluated.

Comparison of cerebral metabolic rate of oxygen, blood flow, and bispectral index under general anesthesia.

In this work, we used a hybrid time domain near-infrared spectroscopy (TD-NIRS) and diffuse correlation spectroscopy (DCS) device to retrieve hemoglobin and blood flow oscillations of skeletal muscle microvasculature. We focused on very low (VLF) and low-frequency (LF) oscillations ( frequency lower than 0.145 Hz), that are related to myogenic, neurogenic and endothelial activities. We measured power spectral density (PSD) of blood flow and hemoglobin concentration in four muscles (thenar eminence, plantar fascia, sternocleidomastoid and forearm) of 14 healthy volunteers to highlight possible differences in microvascular hemodynamic oscillations. We observed larger PSDs for blood flow compared to hemoglobin concentration, in particular in case of distal muscles ( thenar eminence and plantar fascia). Finally, we compared the PSDs measured on the thenar eminence of healthy subjects with the ones measured on a septic patient in the intensive care unit: lower power in the endothelial-dependent frequency band, and larger power in the myogenic ones were observed in the septic patient, in accordance with previous works based on laser doppler flowmetry.

Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies.

In this paper, we present a detailedcharacterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle (SCM), obtained through ultrasound-guided near-infrared time-domain and diffuse correlation spectroscopies.A total of sixty-five subjects (forty-nine females, sixteen males) among healthy volunteers and thyroid nodule patients have been recruited for the study. Their SCM hemodynamic (oxy-, deoxy- and total hemoglobin concentrations, blood flow, blood oxygen saturation and metabolic rate of oxygen extraction) and optical properties (wavelength dependent absorption and reduced scattering coefficients) have been measured by the use of a novel hybrid device combining in a single unit time-domain near-infrared spectroscopy, diffuse correlation spectroscopy and simultaneous ultrasound imaging.We provide detailed tables of the results related to SCM baseline (i.e. muscle at rest) properties, and reveal significant differences on the measured parameters due to variables such as side of the neck, sex, age, body mass index, depth and thickness of the muscle, allowing future clinical studies to take into account such dependencies.The non-invasive monitoring of the hemodynamics and metabolism of the sternocleidomastoid muscle during respiration became a topic of increased interest partially due to the increased use of mechanical ventilation during the COVID-19 pandemic. Near-infrared diffuse optical spectroscopies were proposed as potential practical monitors of increased recruitment of SCM during respiratory distress. They can provide clinically relevant information on the degree of the patient's respiratory effort that is needed to maintain an optimal minute ventilation, with potential clinical application ranging from evaluating chronic pulmonary diseases to more acute settings, such as acute respiratory failure, or to determine the readiness to wean from invasive mechanical ventilation.

characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle through ultrasound-guided hybrid near-infrared spectroscopies.

Article	Year
Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies. PloS one\| PubMed ID: 26815533	2016
Liquid phantoms for near-infrared and diffuse correlation spectroscopies with tunable optical and dynamic properties. Biomedical optics express\| PubMed ID: 29760970	2018
Cerebral oxygenation and blood flow in term infants during postnatal transition: BabyLux project. Archives of disease in childhood. Fetal and neonatal edition\| PubMed ID: 31085677	2019
BabyLux device: a diffuse optical system integrating diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy for the neuromonitoring of the premature newborn brain. Neurophotonics\| PubMed ID: 31093515	2019
Accuracy and precision of tissue optical properties and hemodynamic parameters estimated by the BabyLux device: a hybrid time-resolved near-infrared and diffuse correlation spectroscopy neur... Biomedical optics express\| PubMed ID: 31149383	2019
Validation of diffuse correlation spectroscopy against O-water PET for regional cerebral blood flow measurement in neonatal piglets. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism\| PubMed ID: 31665953	2020
Non-Invasive Estimation of Intracranial Pressure by Diffuse Optics: A Proof-of-Concept Study. Journal of neurotrauma\| PubMed ID: 32460617	2020
Recipes for diffuse correlation spectroscopy instrument design using commonly utilized hardware based on targets for signal-to-noise ratio and precision. Biomedical optics express\| PubMed ID: 34221659	2021
The LUCA device: a multi-modal platform combining diffuse optics and ultrasound imaging for thyroid cancer screening. Biomedical optics express\| PubMed ID: 34221667	2021
Microvascular blood flow changes of the abductor pollicis brevis muscle during sustained static exercise. Biomedical optics express\| PubMed ID: 34457411	2021
Comparison of cerebral metabolic rate of oxygen, blood flow, and bispectral index under general anesthesia. Neurophotonics\| PubMed ID: 36911206	2023
Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies. Biomedical optics express\| PubMed ID: 38021143	2023
characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle through ultrasound-guided hybrid near-infrared spectroscopies. Physiological measurement\| PubMed ID: 38061053	2023

Udo M. Weigel

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