Measures of vascular dysfunction may serve as valuable clinical markers for the early detection of dementia, and for monitoring its progression. Near-Infrared Spectroscopy (NIRS) can non-invasively measure brain oxygenation by quantifying concentration changes of oxygenated (HbO) and deoxygenated haemoglobin (HbR). NIRS shows much promise for clinical translation: it has few contraindications, it can be performed at the bedside, and it is low-cost. High-Density Diffuse Optical Tomography (HD-DOT) extends this method by combining high-density NIRS with anatomical information to produce volumetric or topographical maps of brain oxygenation. Here we present an observational cohort study for Alzheimer's disease, dementia with Lewy bodies or mild cognitive impairment (n=32), which for the first time evaluates the possibility of using HD-DOT to develop biomarkers for dementia. Our early findings show that visual stimulation elicits a reduction in the magnitude of concentration changes of both HbO and HbR in Alzheimer’s Disease compared to healthy controls.
KEYWORDS: Near infrared spectroscopy, Dementia, Brain, Design and modelling, Data modeling, Neuroimaging, Neurodegeneration, Image classification, Head, Magnetic resonance imaging
SignificanceDementia presents a global healthcare crisis, and neuroimaging is the main method for developing effective diagnoses and treatments. Yet currently, there is a lack of sensitive, portable, and low-cost neuroimaging tools. As dementia is associated with vascular and metabolic dysfunction, near-infrared spectroscopy (NIRS) has the potential to fill this gap.AimThis future perspective aims to briefly review the use of NIRS in dementia to date and identify the challenges involved in realizing the full impact of NIRS for dementia research, including device development, study design, and data analysis approaches.ApproachWe briefly appraised the current literature to assess the challenges, giving a critical analysis of the methods used. To assess the sensitivity of different NIRS device configurations to the brain with atrophy (as is common in most forms of dementia), we performed an optical modeling analysis to compare their cortical sensitivity.ResultsThe first NIRS dementia study was published in 1996, and the number of studies has increased over time. In general, these studies identified diminished hemodynamic responses in the frontal lobe and altered functional connectivity in dementia. Our analysis showed that traditional (low-density) NIRS arrays are sensitive to the brain with atrophy (although we see a mean decrease of 22% in the relative brain sensitivity with respect to the healthy brain), but there is a significant improvement (a factor of 50 sensitivity increase) with high-density arrays.ConclusionsNIRS has a bright future in dementia research. Advances in technology – high-density devices and intelligent data analysis—will allow new, naturalistic task designs that may have more clinical relevance and increased reproducibility for longitudinal studies. The portable and low-cost nature of NIRS provides the potential for use in clinical and screening tests.
Significance: Measurement and imaging of hemoglobin oxygenation are used extensively in the detection and diagnosis of disease; however, the applied instruments vary widely in their depth of imaging, spatiotemporal resolution, sensitivity, accuracy, complexity, physical size, and cost. The wide variation in available instrumentation can make it challenging for end users to select the appropriate tools for their application and to understand the relative limitations of different methods.Aim: We aim to provide a systematic overview of the field of hemoglobin imaging and sensing.Approach: We reviewed the sensing and imaging methods used to analyze hemoglobin oxygenation, including pulse oximetry, spectral reflectance imaging, diffuse optical imaging, spectroscopic optical coherence tomography, photoacoustic imaging, and diffuse correlation spectroscopy.Results: We compared and contrasted the ability of different methods to determine hemoglobin biomarkers such as oxygenation while considering factors that influence their practical application.Conclusions: We highlight key limitations in the current state-of-the-art and make suggestions for routes to advance the clinical use and interpretation of hemoglobin oxygenation information.
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.
We present a new optical platform that combines broadband near-infrared spectroscopy and diffuse correlation spectroscopy for identification of brain injury severity in a preclinical model of hypoxic-ischemic encephalopathy of the neonatal brain.
Performance assessment and standardization are indispensable for instruments of clinical relevance in general and clinical instrumentation based on photon migration/diffuse optics in particular. In this direction, a multi-laboratory exercise was initiated with the aim of assessing and comparing their performances. 29 diffuse optical instruments belonging to 11 partner institutions of a European level Marie Curie Consortium BitMap1 were considered for this exercise. The enrolled instruments covered different approaches (continuous wave, CW; frequency domain, FD; time domain, TD and spatial frequency domain imaging, SFDI) and applications (e.g. mammography, oximetry, functional imaging, tissue spectroscopy). 10 different tests from 3 well-accepted protocols, namely, the MEDPHOT2 , the BIP3 , and the nEUROPt4 protocols were chosen for the exercise and the necessary phantoms kits were circulated across labs and institutions enrolled in the study. A brief outline of the methodology of the exercise is presented here. Mainly, the design of some of the synthetic descriptors, (single numeric values used to summarize the result of a test and facilitate comparison between instruments) for some of the tests will be discussed.. Future actions of the exercise aim at deploying these measurements onto an open data repository and investigating common analysis tools for the whole dataset.
We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin ( [ HbO2 ] ) and deoxyhemoglobin ([HHb]) plus tissue metabolism via changes in the oxidation state of cytochrome-c-oxidase ([oxCCO]). The system is based on a small light source and a customized mini-spectrometer. We assessed the instrument in a preclinical study in 27 newborn piglets undergoing transient cerebral hypoxia-ischemia (HI). We aimed to quantify the recovery of the HI insult and estimate the severity of the injury. The recovery in brain oxygenation (Δ [ HbDiff ] = Δ [ HbO2 ] − Δ [ HHb ] ), blood volume (Δ [ HbT ] = Δ [ HbO2 ] + Δ [ HHb ] ), and metabolism (Δ [ oxCCO ] ) for up to 30 min after the end of HI were quantified in percentages using the recovery fraction (RF) algorithm, which quantifies the recovery of a signal with respect to baseline. The receiver operating characteristic analysis was performed on bNIRS-RF measurements compared to proton (H1) magnetic resonance spectroscopic (MRS)-derived thalamic lactate/N-acetylaspartate (Lac/NAA) measured at 24-h post HI insult; Lac/NAA peak area ratio is an accurate surrogate marker of neurodevelopmental outcome in babies with neonatal HI encephalopathy. The Δ [ oxCCO ] -RF cut-off threshold of 79% within 30 min of HI predicted injury severity based on Lac/NAA with high sensitivity (100%) and specificity (93%). A significant difference in thalamic Lac/NAA was noticed (p < 0.0001) between the two groups based on this cut-off threshold of 79% Δ [ oxCCO ] -RF. The severe injury group (n = 13) had ∼30 % smaller recovery in Δ [ HbDiff ] -RF (p = 0.0001) and no significant difference was observed in Δ [ HbT ] -RF between groups. At 48 h post HI, significantly higher P31-MRS-measured inorganic phosphate/exchangeable phosphate pool (epp) (p = 0.01) and reduced phosphocreatine/epp (p = 0.003) were observed in the severe injury group indicating persistent cerebral energy depletion. Based on these results, the bNIRS measurement of the oxCCO recovery fraction offers a noninvasive real-time biomarker of brain injury severity within 30 min following HI insult.
We present a newly developed multichannel broadband NIRS (or bNIRS) system that has the capacity to measure changes in light attenuation of 308 NIR wavelengths (610nm to 918nm) simultaneously over 16 different brain locations. To achieve this the instrument uses a lens based spectrometer with a front-illuminated CCD that has a sensor size of 26.8x26mm. This large CCD detector allows the simultaneous binning of 16 detector fibres. The software uses the UCLn algorithm to quantify the changes in oxy-, deoxy- haemoglobin concentration (HbO2, HHb) and oxidised cytochrome-coxidase (oxCCO) simultaneously over 16 different brain locations with 1second sampling rate. We demonstrate the use of the instrument in quantifying brain tissue oxygenation and metabolic activity simultaneously with electrical changes as measured with EEG in children with seizures.
Brain tissue oxygen saturation, StO2, measured with near-infrared spectroscopy (NIRS) is of great clinical interest as it quantifies the balance between cerebral oxygen supply and demand. Some brain oximeters are based on spatially resolved spectroscopy (SRS), where NIRS data is collected at multiple distances from the light source to estimate a slope of light attenuation against distance. Other use a broadband approach which utilizes derivatives of the absorption spectra to estimate StO2, such as broadband fitting (BF). We describe a novel algorithm, broadband spatially resolved spectroscopy (BB-SRS), for estimating StO2. It is based on comparing the measured slope to a model of the attenuation slope, which depends on the optical properties of tissue. Fitting this model with a least squares fitting procedure recovers parameters describing absorption and scattering; the concentrations of oxy- and deoxy-haemoglobin and hence StO2 and the scattering parameters β and α describing the exponential dependence of scattering on wavelength. To demonstrate BB-SRS, a broadband spectrum (700 - 1000 nm, step size 2 nm) was simulated in NIRFAST and was analysed with BB-SRS, SRS and BF. The developed BB-SRS algorithm recovered StO2 with a relative error of -9%; the concentration of deoxyhaemoglobin with a relative error of +4% , oxyhaemoglobin -10%. The scattering parameters β and α were recovered with a relative error of -30% and -2%, respectively. Among the three algorithms, BB-SRS performed with the best relative error.
KEYWORDS: Near infrared spectroscopy, Positron emission tomography, Tissue optics, Injuries, Magnetic resonance imaging, Tissues, Oxygen, Brain, Medical research
This is the first multimodal study of cerebral tissue metabolism and perfusion post-hypoxic-ischaemic (HI) brain injury with broadband near-infrared spectroscopy (bNIRS), diffuse correlation spectroscopy (DCS), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). In 5 piglet models of HI, we measured cerebral tissue saturation (StO2), cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), changes in the mitochondrial oxidation state of cytochrome-c-oxidase (oxCCO), cerebral glucose metabolism (CMRglc), and tissue biochemistry (Lac+Thr/tNAA). At baseline, the parameters measured were: 64±6 % StO2, 35±11 ml/100g/min CBF, and 2.0±0.4 μmol/100g/min CMRO2. After HI the parameters measured were: 68±6% StO2, 35±6 ml/100g/min CBF, 1.3±0.1 μmol/100g/min CMRO2, 0.4±0.2 Lac+Thr/tNAA, and 9.5±2.0 CMRglc. This study demonstrates the capacity of a multimodal set up to interrogate the pathophysiology of HIE using a combination of optical methods, MRS, and PET.
Broadband near-infrared spectroscopy (NIRS) can provide an endogenous indicator of tissue temperature based on the temperature dependence of the water absorption spectrum. We describe a first evaluation of the calibration and prediction of brain tissue temperature obtained during hypothermia in newborn piglets (animal dataset) and rewarming in newborn infants (human dataset) based on measured body (rectal) temperature. The calibration using partial least squares regression proved to be a reliable method to predict brain tissue temperature with respect to core body temperature in the wavelength interval of 720 to 880 nm with a strong mean predictive power of R2=0.713±0.157 (animal dataset) and R2=0.798±0.087 (human dataset). In addition, we applied regression receiver operating characteristic curves for the first time to evaluate the temperature prediction, which provided an overall mean error bias between NIRS predicted brain temperature and body temperature of 0.436±0.283°C (animal dataset) and 0.162±0.149°C (human dataset). We discuss main methodological aspects, particularly the well-known aspect of over- versus underestimation between brain and body temperature, which is relevant for potential clinical applications.
KEYWORDS: Near infrared spectroscopy, Brain, Oxygen, Mode conditioning cables, Signal attenuation, Tissue optics, Chromophores, Tissues, In vivo imaging, Algorithm development
Near-infrared spectroscopy (NIRS) measurements of cytochrome-c-oxidase (CCO) have the potential to yield crucial information about cerebral metabolism at the patient bedside. Developments in instrumentation and the analytical methods used to resolve changes in CCO have led to many clinical applications of the measurement since its first demonstration in 1977 by Jöbsis. There is a substantial literature of work on measures of CCO in animal and in vitro studies; however, this review focuses on translational studies. Almost 40 years from the advent of the first measurement of CCO using NIRS, this signal continues to hold significant interest in our understanding of the human brain in health and disease. We discuss methodologies for obtaining NIRS measurements of CCO in the clinic and review studies in neonates and adults.
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