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

[This corrects the article on p. 5994 in vol. 14, PMID: 38021143.].

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 practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Time domain diffuse Raman spectroscopy using single pixel detection.

Diffuse Raman spectroscopy (DIRS) extends the high chemical specificity of Raman scattering to in-depth investigation of thick biological tissues. We present here a novel approach for time-domain diffuse Raman spectroscopy (TD-DIRS) based on a single-pixel detector and a digital micromirror device (DMD) within an imaging spectrometer for wavelength encoding. This overcomes the intrinsic complexity and high cost of detection arrays with ps-resolving time capability. Unlike spatially offset Raman spectroscopy (SORS) or frequency offset Raman spectroscopy (FORS), TD-DIRS exploits the time-of-flight distribution of photons to probe the depth of the Raman signal at a single wavelength with a single source-detector separation. We validated the system using a bilayer tissue-bone mimicking phantom composed of a 1 cm thick slab of silicone overlaying a calcium carbonate specimen and demonstrated a high differentiation of the two Raman signals. We reconstructed the Raman spectra of the two layers, offering the potential for improved and quantitative material analysis. Using a bilayer phantom made of porcine muscle and calcium carbonate, we proved that our system can retrieve Raman peaks even in the presence of autofluorescence typical of biomedical tissues. Overall, our novel TD-DIRS setup proposes a cost-effective and high-performance approach for in-depth Raman spectroscopy in diffusive media.

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 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 (i.e., 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 (i.e., 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.

Non-invasive estimation of in vivo optical properties and hemodynamic parameters of domestic animals: a preliminary study on horses, dogs, and sheep.

Biosensors applied in veterinary medicine serve as a noninvasive method to determine the health status of animals and, indirectly, their level of welfare. Near infrared spectroscopy (NIRS) has been suggested as a technology with this application. This study presents preliminary in vivo time domain NIRS measurements of optical properties (absorption coefficient, reduced scattering coefficient, and differential pathlength factor) and hemodynamic parameters (concentration of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin, and tissue oxygen saturation) of tissue domestic animals, specifically of skeletal muscle (4 dogs and 6 horses) and head (4 dogs and 19 sheep). The results suggest that TD NIRS in vivo measurements on domestic animals are feasible, and reveal significant variations in the optical and hemodynamic properties among tissue types and species. In horses the different optical and hemodynamic properties of the measured muscles can be attributed to the presence of a thicker adipose layer over the muscle in the Longissimus Dorsi and in the Gluteus Superficialis as compared to the Triceps Brachii. In dogs the absorption coefficient is higher in the head (temporalis musculature) than in skeletal muscles. The smaller absorption coefficient for the head of the sheep as compared to the head of dogs may suggest that in sheep we are indeed reaching the brain cortex while in dog light penetration can be hindered by the strongly absorbing muscle covering the cranium.

Motor cortex hemodynamic response to goal-oriented and non-goal-oriented tasks in healthy subjects.

Background: Motor disorders are one of the world's major scourges, and neuromotor rehabilitation is paramount for prevention and monitoring plans. In this scenario, exercises and motor tasks to be performed by patients are crucial to follow and assess treatments' progression and efficacy. Nowadays, in clinical environments, quantitative assessment of motor cortex activities during task execution is rare, due to the bulkiness of instrumentation and the need for immobility during measurements [e.g., functional magnetic resonance imaging (MRI)]. Functional near-infrared spectroscopy (fNIRS) can contribute to a better understanding of how neuromotor processes work by measuring motor cortex activity non-invasively in freely moving subjects. Aim: Exploit fNIRS to measure functional activation of the motor cortex area during arm-raising actions. Design: All subjects performed three different upper limbs motor tasks: arm raising (non-goal-oriented), arm raising and grasping (goal oriented), and assisted arm raising (passive task). Each task was repeated ten times. The block design for each task was divided into 5 seconds of baseline, 5 seconds of activity, and 15 seconds of recovery. Population: Sixteen healthy subjects (11 males and 5 females) with an average (+/- standard deviation) of 37.9 (+/- 13.0) years old. Methods: Cerebral hemodynamic responses have been recorded in two locations, motor cortex (activation area) and prefrontal cortex (control location) exploiting commercial time-domain fNIRS devices. Haemodynamic signals were analyzed, separating the brain cortex hemodynamic response from extracerebral hemodynamic variations. Results: The hemodynamic response was recorded in the cortical motor area for goal-oriented and not-goaloriented tasks, while no response was noticed in the control location (prefrontal cortex position). Conclusions: This study provides a basis for canonical upper limb motor cortex activations that can be potentially compared to pathological cerebral responses in patients. It also highlights the potential use of TD-fNIRS to study goal-oriented versus non-goaloriented motor tasks. Impact: the findings of this study may have implications for clinical rehabilitation by providing a better understanding of the neural mechanisms underlying goal-oriented versus non-goal-oriented motor tasks. This may lead to more effective rehabilitation strategies for individuals with motor disorders and a more effective diagnosis of motor dysfunction supported by objective and quantitative neurophysiological readings.

Surface Cranial Ultrasound: The Natural Heir to X-Ray for the Screening of Skull Deformities in Infants.

PURPOSE: Volumetric tomography (3D-CT) is currently considered the gold standard for the diagnosis of craniosynostosis, but its use as the first-line examination for cranial deformities is a topic of debate, because of skull X-ray radiation and low sensitivity and specificity. Cranial ultrasound is an emerging noninvasive radiation-free alternative, but its diagnostic accuracy still needs confirmation. MATERIALS AND METHODS: The present prospective study included 350 infants with skull deformities, who underwent cranial ultrasound as the first-line examination, followed by 3D-CT if the echography results was positive or unclear. If the results were negative, infants underwent physical treatment and follow-up. To evaluate ultrasound reliability, we focused on cases that underwent both the index test and the gold standard and performed a double-blind comparison of the echography and 3D-CT results. RESULTS: Ultrasound documented patent sutures in 293 infants and 9 had inconclusive results. The 293 ultrasound-negative infants were followed clinically: all improved, except 28 that underwent 3D-CT. In all of these cases, 3D-CT confirmed the ultrasonography results (no false negatives). 48 infants showed premature suture closure and underwent 3D-CT: 47 were confirmed (true positive), 1 was false positive. The sensitivity was 100%, the specificity was 99.7%, the positive and negative predictive values were 97.9% and 100%, respectively, the accuracy was 99.7%, and the diagnostic test evaluation was conclusive. CONCLUSION: The study documented the high sensitivity and specificity of echography for the diagnosis of craniosynostosis in a referral center, with better results being achieved before 6 months of age. Major limitations are the loss of diagnostic significance as the child grows and the learning curve needed. The advantages are avoidance of radiation and chance to evaluate the brain at the same time.

Multi-laboratory performance assessment of diffuse optics instruments: the BitMap exercise.

SIGNIFICANCE: Multi-laboratory initiatives are essential in performance assessment and standardization-crucial for bringing biophotonics to mature clinical use-to establish protocols and develop reference tissue phantoms that all will allow universal instrument comparison. AIM: The largest multi-laboratory comparison of performance assessment in near-infrared diffuse optics is presented, involving 28 instruments and 12 institutions on a total of eight experiments based on three consolidated protocols (BIP, MEDPHOT, and NEUROPT) as implemented on three kits of tissue phantoms. A total of 20 synthetic indicators were extracted from the dataset, some of them defined here anew. APPROACH: The exercise stems from the Innovative Training Network BitMap funded by the European Commission and expanded to include other European laboratories. A large variety of diffuse optics instruments were considered, based on different approaches (time domain/frequency domain/continuous wave), at various stages of maturity and designed for different applications (e.g., oximetry, spectroscopy, and imaging). RESULTS: This study highlights a substantial difference in hardware performances (e.g., nine decades in responsivity, four decades in dark count rate, and one decade in temporal resolution). Agreement in the estimates of homogeneous optical properties was within 12% of the median value for half of the systems, with a temporal stability of <5 % over 1 h, and day-to-day reproducibility of <3 % . Other tests encompassed linearity, crosstalk, uncertainty, and detection of optical inhomogeneities. CONCLUSIONS: This extensive multi-laboratory exercise provides a detailed assessment of near-infrared Diffuse optical instruments and can be used for reference grading. The dataset-available soon in an open data repository-can be evaluated in multiple ways, for instance, to compare different analysis tools or study the impact of hardware implementations.

Reproducibility of identical solid phantoms.

SIGNIFICANCE: Tissue-like solid phantoms with identical optical properties, known within tolerant uncertainty, are of crucial importance in diffuse optics for instrumentation assessment, interlaboratory comparison studies, industrial standards, and multicentric clinical trials. AIM: The reproducibility in fabrication of homogeneous solid phantoms is focused based on spectra measurements by instrument comparisons grounded on the time-resolved diffuse optics. APPROACH: Epoxy-resin and silicone phantoms are considered as matrices and both employ three different instruments for time-resolved diffuse spectroscopy within the spectral range of 540 to 1100 nm. In particular, we fabricated two batches of five phantoms each in epoxy resin and silicone. Then, we evaluated the intra- and interbatch variability with respect to the instrument precision, by considering the coefficient of variation (CV) of absorption and reduced scattering coefficients. RESULTS: We observed a similar precision for the three instruments, within 2% for repeated measurements on the same phantom. For epoxy-resin phantoms, the intra- and the interbatch variability reached the instrument precision limit, demonstrating a very good phantom reproducibility. For the silicone phantoms, we observed larger values for intra- and interbatch variability. In particular, at worst, for reduced scattering coefficient interbatch CV was about 5%. CONCLUSIONS: Results suggest that the fabrication of solid phantoms, especially considering epoxy-resin matrix, is highly reproducible, even if they come from different batch fabrications and are measured using different instruments.

Optical characterization of 3D printed PLA and ABS filaments for diffuse optics applications.

The interest for Fused Deposition Modelling (FDM) in the field of Diffuse Optics (DO) is rapidly increasing. The most widespread FDM materials are polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS), thanks to their low cost and easiness-to-print. This is why, in this study, 3D printed samples of PLA and ABS materials were optically characterized in the range from the UV up to the IR wavelengths, in order to test their possible employment for probe construction in DO applications. To this purpose, measurements with Near Infrared Spectroscopy and Diffuse Correlation Spectroscopy techniques were considered. The results obtained show how the material employed for probe construction can negatively affect the quality of DO measurements.

Monitoring the motor cortex hemodynamic response function in freely moving walking subjects: a time-domain fNIRS pilot study.

Significance: This study is a preliminary step toward the identification of a noninvasive and reliable tool for monitoring the presence and progress of gaiting dysfunctions. Aim: We present the results of a pilot study for monitoring the motor cortex hemodynamic response function (HRF) in freely walking subjects, with time-domain functional near-infrared spectroscopy (TD fNIRS). Approach: A compact and wearable single-channel TD fNIRS oximeter was employed. The lower limb motor cortex area of three healthy subjects was monitored while performing two different freely moving gaiting tasks: forward and backward walking. Results: The time course of oxygenated and deoxygenated hemoglobin was measured during the different walking tasks. Brain motor cortex hemodynamic activations have been analyzed throughout an adaptive HRF fitting procedure, showing a greater involvement of motor area in the backward walking task. By comparison with the HRF obtained in a finger-tapping task performed in a still condition, we excluded any effect of motion artifacts in the gaiting tasks. Conclusions: For the first time to our knowledge, the hemodynamic motor cortex response was measured by TD fNIRS during natural, freely walking exercises. The cortical response during forward and backward walking shows differences, possibly related to the diverse involvement of the motor cortex in the two types of gaiting.

A Compact Multi-Distance DCS and Time Domain NIRS Hybrid System for Hemodynamic and Metabolic Measurements.

In this work, we present a new multi-distance diffuse correlation spectroscopy (DCS) device integrated with a compact state-of-the-art time domain near infrared spectroscopy (TD-NIRS) device. The hybrid DCS and TD-NIRS system allows to retrieve information on blood flow, tissue oxygenation, and oxygen metabolic rate. The DCS device performances were estimated in terms of stability, repeatability, ability in retrieving variations of diffusion coefficient, influence of the tissue optical properties, effect of varying count rates and depth sensitivity. Crosstalk between DCS and TD-NIRS optical signals was also evaluated. Finally, in vivo experiments (venous and arterial cuff occlusions on the arm) were conducted to test the ability of the hybrid system in measuring blood flow variations.

Wearable and wireless time-domain near-infrared spectroscopy system for brain and muscle hemodynamic monitoring.

We present a wearable time-domain near infrared spectroscopy (TD-NIRS) system (two wavelengths, one detection channel), which fits in a backpack and performs real-time hemodynamic measurements on the brain and muscle tissues of freely moving subjects. It can provide concentration values of oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), total hemoglobin (tHb = O2Hb + HHb) and tissue oxygen saturation (StO2). The system is battery-operated and can be wirelessly controlled. By following established characterization protocols for performance assessment of diffuse optics instruments, we achieved results comparable with state-of-the-art research-grade TD-NIRS systems. We also performed in-vivo measurements such as finger tapping (motor cortex monitoring), breath holding (prefrontal cortex monitoring and forearm muscle monitoring), and outdoor bike riding (vastus lateralis muscle monitoring), in order to test the system capabilities in evaluating both muscle and brain hemodynamics.