Functional near-infrared spectroscopy (fNIRS) has been utilized already around three decades for monitoring the brain, in particular, oxygenation changes in the cerebral cortex. In addition, other optical techniques are currently developed for in vivo imaging and in the near future can be potentially used more in human brain research. This paper reviews the most common label-free optical technologies exploited in brain monitoring and their current and potential clinical applications. Label-free tissue monitoring techniques do not require the addition of dyes or molecular contrast agents. The following optical techniques are considered: fNIRS, diffuse correlations spectroscopy (DCS), photoacoustic imaging (PAI) and optical coherence tomography (OCT). Furthermore, wearable optical brain monitoring with the most common applications is discussed.
In this chapter, we review state-of-the-art non-invasive techniques to monitor and study cerebral circulation in humans. The measurement methods can be divided into two categories: direct and indirect methods. Direct methods are mostly based on using contrast agents delivered to blood circulation. Clinically used direct methods include single-photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI) with contrast agents, xenon computed tomography (CT), and arterial spin labeling (ASL) MRI. Indirect techniques are based on measuring physiological parameters reflecting cerebral perfusion. The most commonly used indirect methods are near-infrared spectroscopy (NIRS), transcranial Doppler ultrasound (TCD), and phase-contrast MRI. In recent years, few more techniques have been intensively developed, such as diffuse correlation spectroscopy (DCS) and microwave-based techniques, which are still emerging as methods for cerebral circulation monitoring. In addition, methods combining different modalities are discussed and, as a summary, the presented techniques and their benefits for cerebral circulation will be compared.
Functional near-infrared spectroscopy (fNIRS) is commonly used as a non-invasive tool to measure cerebral neurovascular dynamics. Its potential for diagnostics of various brain disorders has been already demonstrated in many recent studies, including Alzheimer’s disease (AD). fNIRS studies are usually based on comparing hemoglobin measurements at baseline and during a specific task. At present, many proposed methods using fNIRS to diagnose AD involve certain tasks, which may be challenging for the elderly and patients with cognitive decline. Here, we propose a method to characterize AD patients and control in resting state, by applying spectral entropy (SE) analysis on oxyhemoglobin and deoxyhemoglobin, HbO and HbR, respectively, and total hemoglobin (HbT) based on fNIRS signals measured from the left and right sides of the forehead. We applied SE to very low frequency (VLF) (0.008–0.1 Hz), respiratory (0.1–0.6 Hz), and cardiac (0.6–5 Hz) bands to find out which band delivered the optimum result. Next, a t test with 0.05 significant level was performed to compare SE values of AD patients and controls. Results from the VLF band looked promising as SE values from AD patients were always significantly higher than those from controls. In addition, this phenomenon was consistent for both sides of the forehead. However, significant differences in SE values in the respiratory band were found from the left hemisphere only, and in the cardiac band from the right hemisphere only. SE value from the VLF band supports a strong argument that it provides good predictability related to the development of AD. We demonstrated that SE of brain fNIRS signal can be an useful biomarker for Alzheimer’s disease pathology.
Functional magnetic resonance imaging (fMRI) is a common medical device to diagnose Alzheimer's disease (AD), but it is not for all subjects due to its cost and other issues. We investigated the potential of functional near-infrared spectroscopy (fNIRS) to separate AD patients from controls as a pre-screening prior to more thorough examination using fMRI. For this purpose, two-channel fNIRS device with 690 nm and 830 nm, sampled at 10 Hz, was placed on the forehead with 3 cm distance between light source and detector to provide resting state fNIRS signals from both sides of pre-frontal cortex. We applied fractional amplitude of physiological fluctuation (fAPF), modified from fractional amplitude of low frequency fluctuation (fALFF), to oxy-, deoxy-, and total-hemoglobin in very low frequency (0.008-0.1 Hz), respiratory (0.1-0.6 Hz), and cardiac (0.6-5 Hz) bands. A t-test at 0.05 significance level was used to evaluate if the fAPF score from AD patients and healthy controls is significantly different. We found that fAPF score of total hemoglobin from both side at cardiac band showed its potential to distinguish AD patients from healthy controls. This finding was in-line with the recent finding that heart failure may co-occur in AD patients with the prevalence of one third of cases.
Background Inside the incompressible cranium, the volume of cerebrospinal fluid (CSF) is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering (BPL) on fluorescent CSF tracer absorption into the systemic blood circulation. Methods BPL was performed by an i.v. administration of nitric oxide donor sodium nitroprusside (5 μg kg-1 min-1) or the Ca2+-channel blocker nicardipine hydrochloride (0.5 μg kg-1 min-1) for 10 and 15 to 40 mins, respectively. The effect of BPL on CSF clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. Results Nicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 22.0 ± 2.5%, while temporarily elevating in intracranial pressure by 14.0 ± 6.0% and 11.6 ± 2.0%, respectively. BPL significantly increased tracer accumulation into deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by BPL into the systemic circulation was markedly reduced (-66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes. Conclusions This is the first study showing that CSF clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced CSF clearance by BPL may have therapeutic potential in diseases with dysregulated CSF flow.
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