Time-domain Near-infrared Spectroscopy Research Articles

A personalized clinical assessment: multi-sensor approach for understanding musculoskeletal health in the frail population

BackgroundSarcopenia is a muscle disorder causing a progressive reduction of muscle mass and strength, but the mechanism of its manifestation is still partially unknown. The three main parameters to assess are: muscle strength, muscle volume or quality and low physical performance. There is not a definitive approach to assess the musculoskeletal condition of frail population and often the available tests to be performed in those clinical bedridden patients is reduced because of physical impairments. In this paper, we propose a novel instrumental multi-domain and non-invasive approach during a well-defined protocol of measurements for overcoming these limitations. A group of 28 bedridden elder people, subjected to surgery after hip fracture, was asked to perform voluntary isometric contractions at the 80% of their maximum voluntary contraction with the non-injured leg. The sensor employed before and/or during the exercise were: ultrasound to determine the muscle architecture (vastus lateralis); force acquisition with a load cell placed on the chair, giving an indication of the muscle strength; surface electromyography (EMG) for monitoring muscular electrical activity; time-domain (TD) near-infrared spectroscopy (NIRS) for evaluating muscle oxidative metabolism.ResultsA personalized “report card” for each subject was created. It includes: the force diagram (both instantaneous and cumulative, expected and measured); the EMG–force diagram for a comparison between EMG derived median frequency and measured force; two graphs related to the hemodynamic parameters for muscle oxidative metabolism evaluation, i.e., oxy-, deoxy-, total-hemoglobin and tissue oxygen saturation for the whole exercise period. A table with the absolute values of the previous hemodynamic parameters during the rest and the ultrasound related parameters are also included.ConclusionsIn this work, we present the union of protocols, multi-domain sensors and parameters for the evaluation of the musculoskeletal condition. The novelties are the use of sensors of different nature, i.e., force, electrical and optical, together with a new way to visualize and combine the results, by means of a concise, exhaustive and personalized medical report card for each patient. This assessment, totally non-invasive, is focused on a bedridden population, but can be extended to the monitoring of rehabilitation progresses or of the training of athletes.

Investigating cortical hypoxia in multiple sclerosis via time-domain near-infrared spectroscopy.

Hypoperfusion and tissue hypoxia have been implicated as contributory mechanisms in the neuropathology of multiple sclerosis (MS). Our objective has been to study cortical oxygenation in vivo in patients with MS and age-matched controls. A custom, multiwavelength time-domain near-infrared spectroscopy system was developed for assessing tissue hypoxia from the prefrontal cortex. A cross-sectional case-control study was undertaken assessing patients with secondary progressive MS (SPMS) and age-matched controls. Co-registered magnetic resonance imaging was used to verify the location from which near-infrared spectroscopy data were obtained through Monte Carlo simulations of photon propagation. Additional clinical assessments of MS disease severity were carried out by trained neurologists. Linear mixed effect models were used to compare cortical oxygenation between cases and controls, and against measures of MS severity. Thirty-three patients with secondary progressive MS (median expanded disability status scale 6 [IQR: 5-6.5]; median age 53.0 [IQR: 49-58]) and 20 age-matched controls were recruited. Modeling of photon propagation confirmed spectroscopy data were obtained from the prefrontal cortex. Patients with SPMS had significantly lower cortical hemoglobin oxygenation compared with controls (-6.0% [95% CI: -10.0 to -1.9], P = 0.004). There were no significant associations between cortical oxygenation and MS severity. Using an advanced, multiwavelength time-domain near-infrared spectroscopy system, we demonstrate that patients with SPMS have lower cortical oxygenation compared with controls.

Time-resolved near-infrared spectroscopy in monitoring acute ischemic stroke patients – Case study

Stroke is a leading cause of disability and death worldwide, with acute ischemic stroke (AIS) accounting for the majority of cases. Early and accurate diagnosis of AIS is crucial for improving patient outcomes. Non-invasive monitoring techniques, such as time domain near-infrared spectroscopy (tdNIRS), have shown potential for real-time monitoring of AIS patients at the bedside. However, there is a need for further research to evaluate the effectiveness of tdNIRS in the acute phase of stroke. In this study, we present the results of a case report using tdNIRS to monitor AIS patients without any additional stimulation. The tdNIRS technique allows for non-invasively assessing cerebral oxygenation in absolute units, enabling accurate measurement of changes in oxygenated and deoxygenated hemoglobin concentrations in the brain. Our aim was to determine the feasibility of tdNIRS in monitoring AIS patients.

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

Objective. In this paper, we present a detailed in vivo characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle (SCM), obtained through ultrasound-guided near-infrared time-domain and diffuse correlation spectroscopies. Approach. 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. Main results. 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. Significance. 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.

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.

Two-layered blood-lipid phantom and method to determine absorption and oxygenation employing changes in moments of DTOFs.

Near-infrared spectroscopy (NIRS) is an established technique for measuring tissue oxygen saturation (StO2), which is of high clinical value. For tissues that have layered structures, it is challenging but clinically relevant to obtain StO2 of the different layers, e.g. brain and scalp. For this aim, we present a new method of data analysis for time-domain NIRS (TD-NIRS) and a new two-layered blood-lipid phantom. The new analysis method enables accurate determination of even large changes of the absorption coefficient (Δµa) in multiple layers. By adding Δµa to the baseline µa, this method provides absolute µa and hence StO2 in multiple layers. The method utilizes (i) changes in statistical moments of the distributions of times of flight of photons (DTOFs), (ii) an analytical solution of the diffusion equation for an N-layered medium, (iii) and the Levenberg-Marquardt algorithm (LMA) to determine Δµa in multiple layers from the changes in moments. The method is suitable for NIRS tissue oximetry (relying on µa) as well as functional NIRS (fNIRS) applications (relying on Δµa). Experiments were conducted on a new phantom, which enabled us to simulate dynamic StO2 changes in two layers for the first time. Two separate compartments, which mimic superficial and deep layers, hold blood-lipid mixtures that can be deoxygenated (using yeast) and oxygenated (by bubbling oxygen) independently. Simultaneous NIRS measurements can be performed on the two-layered medium (variable superficial layer thickness, L), the deep (homogeneous), and/or the superficial (homogeneous). In two experiments involving ink, we increased the nominal µa in one of two compartments from 0.05 to 0.25 cm-1, L set to 14.5 mm. In three experiments involving blood (L set to 12, 15, or 17 mm), we used a protocol consisting of six deoxygenation cycles. A state-of-the-art multi-wavelength TD-NIRS system measured simultaneously on the two-layered medium, as well as on the deep compartment for a reference. The new method accurately determined µa (and hence StO2) in both compartments. The method is a significant progress in overcoming the contamination from the superficial layer, which is beneficial for NIRS and fNIRS applications, and may improve the determination of StO2 in the brain from measurements on the head. The advanced phantom may assist in the ongoing effort towards more realistic standardized performance tests in NIRS tissue oximetry. Data and MATLAB codes used in this study were made publicly available.

Association between regional cerebral oxygen saturation and outcome of patients with out-of-hospital cardiac arrest: An observational study

AimThis study aimed to evaluate the association between cerebral oxygen saturation (StO2) and return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA). MethodsWe retrospectively evaluated the data of patients with OHCA to determine the association between ROSC and various StO2 parameters (initial_StO2, final_StO2, mean_StO2, and Δ_StO2 [=final_StO2-initial_StO2]). Time-domain near-infrared spectroscopy was used to determine absolute StO2 values. ResultsOf the 108 patients with OHCA, 23 achieved ROSC. Although initial_StO2 values did not differ between the groups, final_StO2, mean_StO2, and Δ_StO2 were higher in the ROSC group than in the non-ROSC group. The cut-off values for initial_StO2, mean_StO2, and Δ_StO2 as predictors of ROSC were 35%, 30%, and 5%, respectively. The odds ratio for ROSC had markedly increased in the Δ_StO2 ≥ 5% subgroup (19.70 [6.06–64.11], p < 0.001). When the change in StO2 (=d_StO2) at 8 min from the initiation of StO2 measurement was assessed, the d_StO2 ≥ 5% subgroup had a higher odds ratio for ROSC than the d_StO2 < 5% subgroup (5.8 [1.78–18.85], p = 0.002), and this tendency was maintained until 20 min. In the evaluation using a two-by-two contingency table with initial_StO2 and Δ_StO2 as two parameters, 61.9% of the patients fell under the categories of initial_StO2 < 35% and Δ_StO2 < 5% and had the lowest rate of ROSC achievement (4.6%). In the Δ_StO2 ≥ 5% subgroup, approximately-two-thirds of the patients achieved ROSC irrespective of the initial_StO2 (initial_StO2 ≥ 35%, 66.7%; initial_StO2 < 35%, 60.0%). ConclusionsInitial_StO2 and Δ_StO2 were associated with the achievement of ROSC.

Upper Trapezius Muscle Tonicity, Assessed by Palpation, Relates to Change in Tissue Oxygenation and Structure as Measured byTime-Domain Near Infrared Spectroscopy.

Palpation is a diagnostic tool widely used by manual therapists despite its disputed reliability and validity. Previous studies have usually focused on the detection of myofascial trigger points (MTrPs), i.e., the points within muscles thought to have undergone molecular composition, oxygenation and structural changes, altering their tonicity. Time-domain near-infrared spectroscopy (TD-NIRS) could provide new insights into soft tissue oxygenation and structure, in order to objectively assess the validity and reliability of palpation. This pilot study aims at (1) assessing the ability of TD-NIRS to detect a difference between palpably normal and hypertonic upper trapezius (UT) muscles, and (2) to estimate the reproducibility of the TD-NIRS measurement on UT muscles. TD-NIRS measurements were performed on 4 points of the UT muscles in 18 healthy participants (10F, mean age: 27.6years), after a physical examination by a student osteopath to locate these points and identify the most and least hypertonic. From TD-NIRS, the most hypertonic points had a higher concentration in deoxy- ([HHb]) (0.887±0.253μM, p<0.001) and total haemoglobin ([HbT]) (1.447±0.772μM, p<0.001), a lower tissue oxygen saturation (StO2) (-0.575±0.286%, p<0.001), and a greater scattering amplitude factor (AF) (0.2238±0.1343 cm-1, p=0.001) than the least hypertonic points. Moreover, the intraclass correlation coefficient one-way random-effects model (ICC (1,1)) calculated for each TD-NIRS parameter and for each point revealed an excellent reliability of the measurement (Mean±SD, 0.9253±0.0678). These initial results, showing that changes in TD-NIRS parameters correlate with changes in muscle tonicity as assessed by palpation, are encouraging and show that TD-NIRS could help to further assess the validity of palpation as a diagnostic tool in manual therapy.

Time-domain NIRS system based on supercontinuum light source and multi-wavelength detection: validation for tissue oxygenation studies.

We present and validate a multi-wavelength time-domain near-infrared spectroscopy (TD-NIRS) system that avoids switching wavelengths and instead exploits the full capability of a supercontinuum light source by emitting and acquiring signals for the whole chosen range of wavelengths. The system was designed for muscle and brain oxygenation monitoring in a clinical environment. A pulsed supercontinuum laser emits broadband light and each of two detection modules acquires the distributions of times of flight of photons (DTOFs) for 16 spectral channels (used width 12.5 nm / channel), providing a total of 32 DTOFs at up to 3 Hz. Two emitting fibers and two detection fiber bundles allow simultaneous measurements at two positions on the tissue or at two source-detector separations. Three established protocols (BIP, MEDPHOT, and nEUROPt) were used to quantitatively assess the system’s performance, including linearity, coupling, accuracy, and depth sensitivity. Measurements were performed on 32 homogeneous phantoms and two inhomogeneous phantoms (solid and liquid). Furthermore, measurements on two blood-lipid phantoms with a varied amount of blood and Intralipid provide the strongest validation for accurate tissue oximetry. The retrieved hemoglobin concentrations and oxygen saturation match well with the reference values that were obtained using a commercially available NIRS system (OxiplexTS) and a blood gas analyzer (ABL90 FLEX), except a discrepancy occurs for the lowest amount of Intralipid. In-vivo measurements on the forearm of three healthy volunteers during arterial (250 mmHg) and venous (60 mmHg) cuff occlusions provide an example of tissue monitoring during the expected hemodynamic changes that follow previously well-described physiologies. All results, including quantitative parameters, can be compared to other systems that report similar tests. Overall, the presented TD-NIRS system has an exemplary performance evaluated with state-of-the-art performance assessment methods.

Towards Development of LED-Based Time-Domain Near-IR Spectroscopy System for Delineating Breast Cancer From Adjacent Normal Tissue

Currently, the breast cancer diagnosis is performed by microscopic examination of thin slices of ex-vivo biopsy tissue by the pathologist. In this paper, a robust and affordable LED-based time-domain near-infrared spectroscopy system (Spectro-IRTDx) is proposed to further aid the pathologist for rapid and accurate breast cancer diagnosis. The measurements are performed on formalin-fixed cancerous tissues (invasive ductal carcinoma) and their adjacent normal tissues obtained from N = 6 patients. The mean effective attenuation coefficient ( μ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><i>eff</i></sub> ) for cancerous tissue is found to be 5.41 and 2.41 times higher than adjacent normal tissue, with good statistical significance (p = 0.00216) while operating at 850 nm and 940 nm, respectively. The average detected peak voltage (DPV) for adjacent normal tissue is found to be 3.44 and 4.16 times higher than cancerous tissue, with good statistical significance (p = 0.00216) while operating at 850 nm and 940 nm, respectively. The mean time of flight for cancerous tissue was 46 ns and 4 ns higher than the adjacent normal tissue while operating at 850 nm and 940 nm, respectively, with good statistical significance (p = 0.00216) at 850 nm. The obtained results establish the proof-of-concept of the time-domain near-infrared spectroscopy for rapid diagnosis of core biopsy tissues.

Time-Domain Near-Infrared Spectroscopy in Subjects with Asymptomatic Cerebral Small Vessel Disease

Biomarkers of microcirculation dysfunction may help in the study of cerebral small vessel disease (CSVD). Time-Domain Near-Infrared spectroscopy (TD-NIRS), estimating the oxygenation of microcirculation of cerebral outer layers, might indirectly correlate with CSVD. We retrospectively evaluated TD-NIRS data from healthy subjects with age ≥ 55 years; no history of brain disease; normal neurological examination; absence of stenosis &gt; 50% of extra/intra-cranial arteries; incidental finding of asymptomatic CSVD at brain magnetic resonance imaging (MRI). According to Fazekas scale, subjects were classified by presence of white matter hyperintensities in periventricular region (pvWMHs), deep white matter region (dWMHs), or both (d+pvWMHs). We compared the concentration of hemoglobin species and tissue oxygen saturation (StO2) among these groups. The study included 20 subjects, median age 67.5 (IQR 61–78) years old (6 without WMHs, 5 with pvWMHs, 9 with d+pvWMHs). Subjects with d+pvWMHs had significantly lower StO2 compared to subjects without WMHs (p = 0.022) or with pvWMHs (p = 0.004). StO2 &lt; 56.7% indicated the presence of d+pvWMHs with 91% sensitivity and 67% specificity [AUC 91% (CI 95% 78–100%)]. In this preliminary study, cerebral TD-NIRS detected significantly lower StO2 in subjects with radiological signs of asymptomatic CSVD. Further studies are needed to evaluate if StO2 might represent a marker of asymptomatic CSVD.

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.

Large-Area, Fast-Gated Digital SiPM With Integrated TDC for Portable and Wearable Time-Domain NIRS

We present the design and characterization of a large-area, fast-gated, all-digital single-photon detector with programmable active area, internal gate generator, and time-to-digital converter (TDC) with a built-in histogram builder circuit, suitable for performing high-sensitivity time-domain near-infrared spectroscopy (TD-NIRS) measurements when coupled with pulsed laser sources. We used a novel low-power differential sensing technique that optimizes area occupation. The photodetector is a time-gated digital silicon photomultiplier (dSiPM) with an 8.6-mm2 photosensitive area, 37% fill-factor, and ~300 ps (20%–80%) gate rising edge, based on low-noise single-photon avalanche diodes (SPADs) and fabricated in 0.35- $\mu \text{m}$ CMOS technology. The built-in TDC with a histogram builder has a least-significant-bit (LSB) of 78 ps and 128 time-bins, and the integrated circuit can be interfaced directly with a low-cost microcontroller with a serial interface for programming and readout. Experimental characterization demonstrated a temporal response as good as 300-ps full-width at half-maximum (FWHM) and a dynamic range >100 dB (thanks to the programmable active area size). This microelectronic detector paves the way for a miniaturized, stand-alone, multi-wavelength TD-NIRS system with an unprecedented level of integration and responsivity, suitable for portable and wearable systems.

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.

Clinical Brain Monitoring with Time Domain NIRS: A Review and Future Perspectives

Near-infrared spectroscopy (NIRS) is an optical technique that can measure brain tissue oxygenation and haemodynamics in real-time and at the patient bedside allowing medical doctors to access important physiological information. However, despite this, the use of NIRS in a clinical environment is hindered due to limitations, such as poor reproducibility, lack of depth sensitivity and poor brain-specificity. Time domain NIRS (or TD-NIRS) can resolve these issues and offer detailed information of the optical properties of the tissue, allowing better physiological information to be retrieved. This is achieved at the cost of increased instrument complexity, operation complexity and price. In this review, we focus on brain monitoring clinical applications of TD-NIRS. A total of 52 publications were identified, spanning the fields of neonatal imaging, stroke assessment, traumatic brain injury (TBI) assessment, brain death assessment, psychiatry, peroperative care, neuronal disorders assessment and communication with patient with locked-in syndrome. In all the publications, the advantages of the TD-NIRS measurement to (1) extract absolute values of haemoglobin concentration and tissue oxygen saturation, (2) assess the reduced scattering coefficient, and (3) separate between extra-cerebral and cerebral tissues, are highlighted; and emphasize the utility of TD-NIRS in a clinical context. In the last sections of this review, we explore the recent developments of TD-NIRS, in terms of instrumentation and methodologies that might impact and broaden its use in the hospital.

Time-Domain Near-Infrared Spectroscopy and Imaging: A Review

This article reviews the past and current statuses of time-domain near-infrared spectroscopy (TD-NIRS) and imaging. Although time-domain technology is not yet widely employed due to its drawbacks of being cumbersome, bulky, and very expensive compared to commercial continuous wave (CW) and frequency-domain (FD) fNIRS systems, TD-NIRS has great advantages over CW and FD systems because time-resolved data measured by TD systems contain the richest information about optical properties inside measured objects. This article focuses on reviewing the theoretical background, advanced theories and methods, instruments, and studies on clinical applications for TD-NIRS including some clinical studies which used TD-NIRS systems. Major events in the development of TD-NIRS and imaging are identified and summarized in chronological tables and figures. Finally, prospects for TD-NIRS in the near future are briefly described.

Time-domain near-infrared spectroscopy in acute ischemic stroke patients.

Large vessel occlusion (LVO) stroke might cause different degrees of hemodynamic impairment that affects microcirculation and contributes to metabolic derangement. Time-domain near-infrared spectroscopy (TD-NIRS) estimates the oxygenation of microcirculation of cerebral outer layers. We measure hemoglobin species and tissue oxygen saturation ( ) of anterior circulation stroke patients, classified as LVO or lacunar, and assess the differences compared with controls and according to LVO recanalization status. Fiducial markers categorize the brain region below each TD-NIRS probe as ischemic or nonstroke areas. The study includes 47 consecutive acute ischemic stroke patients and 35 controls. The ischemic area has significantly higher deoxy-hemoglobin (HbR) and total hemoglobin (HbT) compared with controls in both recanalized and nonrecanalized patients but lower only in recanalized patients. Recanalized patients have significantly lower mean in the ipsilateral hemisphere compared with nonrecanalized patients. This is the first study to report TD-NIRS measurements in acute ischemic stroke patients. TD-NIRS is able to detect significant differences in hemoglobin species in LVO stroke compared with controls and according to recanalization status. This preliminary data might suggest that can serve as a surrogate functional marker of the metabolic activity of rescued brain tissue.

Abstract TP81: Time-Domain Near-Infrared Spectroscopy in Acute Ischemic Stroke Patients

Background: cerebral microcirculation might reveal important prognostic information for acute ischemic stroke. Time-Domain Near-Infrared Spectroscopy (TD-NIRS) is an advanced optical technique that estimates quantitatively and non-invasively the oxygenation in microcirculation of cerebral outer layers at the bedside of the patient. We aimed to measure hemoglobin species and tissue oxygen saturation in acute ischemic stroke patients comparing them to controls according to brain areas and large vessel recanalization status. Methods: TD-NIRS measurements within 24 h of stroke onset (1 st time point) and after 24 h (2 nd time point) were performed on anterior circulation stroke patients classified as lacunar and recanalized or non-recanalized partial/total anterior circulation syndrome. Fiducial markers categorized the brain region below each TD-NIRS probe as ischemic or non-stroke areas. We evaluated the concentration of deoxyhemoglobin (HbR), oxyhemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation (StO 2 ) and assessed differences compared to control subjects and according to large vessel occlusion. Results: TD-NIRS measurements were performed on 47 acute ischemic stroke patients. At 1 st time point the ischemic area had higher HbR and HbT compared to controls in both recanalized (p=8.2·10 -4 ; p=0.03) and non-recanalized patients (p=4.9·10 -3 , p=0.03), but lower StO 2 only in recanalized patients (p=0.015). The ischemic area of recanalized patients had higher concentration of HbR, HbO, HbT compared to the ipsilateral non-stroke area (p=0.01; p=3.6·10 -3 ; p=2.0·10 -3 ). The same pattern was observed at 2 nd time point. Recanalized patients had lower mean StO 2 in the ipsilateral hemisphere compared to non-recanalized patients at both time points (p=0.016, p=0.011). Conclusions: TD-NIRS can be performed during routine Stroke Unit activity and it is able to detect significant differences in hemoglobin species in large vessels ischemic stroke patients compared to controls. Data suggest that StO 2 could serve as surrogate functional marker of the metabolic activity of the rescued brain tissue.

Frequency analysis of oscillations in cerebral hemodynamics measured by time domain near infrared spectroscopy.

In this paper, we propose the application of time-domain near-infrared spectroscopy to the assessment of oscillations in cerebral hemodynamics. These oscillations were observed in the statistical moments of the distributions of time of flight of photons (DTOFs) measured on the head. We analyzed the zeroth and second centralized moments of DTOFs (total number of photons and variance) to obtain their spectra to provide parameters for the frequency components of microcirculation, which differ between the extracerebral and intracerebral layers of the head. Analysis of these moments revealed statistically significant differences between a control group of healthy subjects and a group of patients with severe neurovascular disorders, which is a promising result for the assessment of cerebral microcirculation and cerebral autoregulation mechanisms.

A spread spectrum approach to time-domain near-infrared diffuse optical imaging using inexpensive optical transceiver modules.

We introduce a compact time-domain system for near-infrared spectroscopy using a spread spectrum technique. The proof-of-concept single channel instrument utilises a low-cost commercially available optical transceiver module as a light source, controlled by a Kintex 7 field programmable gate array (FPGA). The FPGA modulates the optical transceiver with maximum-length sequences at line rates up to 10Gb/s, allowing us to achieve an instrument response function with full width at half maximum under 600ps. The instrument is characterised through a set of detailed phantom measurements as well as proof-of-concept in vivo measurements, demonstrating performance comparable with conventional pulsed time-domain near-infrared spectroscopy systems.