2020-04-03-功能性光学脑成像

layout	title	subtitle	date	author	header-img	catalog	istop	music-id	music-idfull	apserver	aptype	apsongid	tags
post	功能性光学脑成像	Functional Optical Brain Imaging	2020-04-03	陈锐CR	img/post-bg-cook.jpg	true				netease	song	30780496	fNIRS fNIR 近红外脑成像

Functional Optical Brain Imaging

本文是从《Biomedical Signals, Imaging, andInformatics》摘录，本章节作者 Meltem Izzetoglu，Drexel University。在此感谢作者及相关人的辛勤付出。

6.1 Introduction

Functional imaging is typically conducted in an effort to understand the activity in a given brain region in terms of its relationship to a particular behavioral state, or its interactions with inputs from another region’s activity. The advances in noninvasive functional brain monitoring technologies provide opportunities to accurately examine the living brains of large groups of subjects over long periods of time, with little impact on their well-being. Neurophysiological and neuroimaging technologies have contributed much to our understanding of normative brain function, as well as to our understanding of the neural underpinnings of various neurological and psychiatric disorders. Commonly employed techniques such as electroencephalography (EEG), event-related brain potentials (ERPs), magnetoencephalography (MEG), positron emission tomography (PET), single-positron emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI), have dramatically increased our understanding of a broad range of brain disorders. Nevertheless, there is still much unknown about these syndromes. This is due, in large part, to the inherent complexity of the neurobiological substrates of these disorders and of the mind itself. In addition, each of the research methods used to study brain function and its disorders have methodological strengths as well as their own inherent limitations. These limitations place constraints on our ability to fully explicate the neural basis of neurological and psychiatric disorders both inside and outside of the laboratory setting, and to use the information gleaned from laboratory studies for clinical applications in real-world environments. New techniques that allow data to be gathered under more diverse circumstances than is possible with extant neuroimaging systems should facilitate a more thorough understanding of brain function and its pathologies.

Functional near-infrared spectroscopy (fNIR) has been introduced as a new neuroimaging modality with which to conduct functional brain imaging studies [1–24]. fNIR technology uses specific wavelengths of light, irradiated through the scalp, to enable the noninvasive measurement of changes in the relative ratios of deoxygenated hemoglobin (deoxy-Hb) and oxygenated hemoglobin (oxy-Hb) during brain activity. This technology allows the design of portable, safe, affordable, noninvasive, and minimally intrusive monitoring systems. These qualities make fNIR suitable for the study of hemodynamic changes due to cognitive and emotional brain activity under many working and educational conditions, as well as in the field. Using this technique, several types of brain activity have been assessed, including motor activity, visual activation, auditory stimulation, and the performance of cognitive tasks (e.g., [9]). To date, the outcomes of studies utilizing fNIR compare favorably with previous fMRI and complement EEG findings [21–23].

The purpose of the present chapter is to describe an emerging neuroimaging technology, fNIR, which has several attributes that make it possible to conduct neuroimaging studies of the cortex in clinical offices and under more realistic, ecologically valid parameters. In this chapter, we will first describe general working principles of fNIR and different fNIR instrumentations based on these working principles. Then, we will review algorithms developed for fNIR data processing for artifact removal and used in the extraction of hemodynamic signals from the fNIR intensity measurements. We will discuss the results of various fNIR applications in laboratory settings and in field conditions. Finally, the merits of optical imaging in brain research will be summarized.

6.2 Working Principles

6.2.1 Physiological Principles: How Can Brain Activity Be Measured through Hemodynamic Changes?

Neural activity has a direct relation with hemodynamic changes in the brain [25]. Research on brainenergy metabolism has elucidated the close link between hemodynamic and neural activity [26,27]. Understanding the brain energy metabolism and associated neural activity is of importance for realizing principles of fNIR in assessing brain activity. The brain has small energy reserves and a great majority of the energy used by brain cells is for processes that sustain physiological functioning [28]. Ames III reviewed the studies on brain energy metabolism as related to function and reported that the oxygen (O2) consumption of the rabbit vagus nerve increased 3.4-fold when it was stimulated at 10 Hz and O2 consumption in rabbit sympathetic ganglia increased 40% with stimulation at 15 Hz. Furthermore, glucose utilization by various brain regions increased several fold in response to physiological stimulation or in response to pharmacological agents that affect physiological activity [28]. These studies provide clear evidence that large changes occur in brain energy metabolism in response to changes in activity. The levels of compounds involved in energy metabolism and energy metabolites can be outlined as

• Neuronal activity is fueled by glucose metabolism, so increases in neural activity result in increased glucose and oxygen consumption from the local capillary bed. Brain cells consume energy when activated and oxygen is required to metabolize the glucose. The oxygen concentration in the capillaries can support the normal oxygen consumption (about 3.5 μmol g−1 min−1) for 2 s. [27]. For that reason, a reduction in local glucose and oxygen stimulates the brain to increase local arteriolar vasodilation, which increases local cerebral blood flow (CBF) and cerebral blood volume (CBV), a mechanism known as neurovascular coupling.

• Over a period of several seconds, the increased CBF carries both glucose and oxygen to the neural tissue in the area. Oxygen is transported via oxy-Hb in the blood. The oxygen exchange occurs in the capillary beds. As oxy-Hb gives up oxygen, it is transformed into deoxy-Hb.

• The increased oxygen transported to the area via increased CBF typically exceeds the local neuronal rate of oxygen utilization, the cerebral metabolic rate of oxygen (CMRO2), resulting in an overabundance of cerebral blood oxygenation in active areas [29]. Therefore, local blood is more oxygenated and hence less deoxy-Hb is present [30]. (Although the initial increase in neural activity is thought to result in a focal increase in deoxygenated hemoglobin in the capillary bed as oxygen is withdrawn from the hemoglobin for use in the metabolization of glucose, this feature of the vascular response has been much more difficult to measure, and more controversial, than hyperoxygenation. Please see [31,32], for a more detailed discussion of this topic.) These changes in the hemodynamic signals occur within a few seconds after the onset of the stimulation and may take 10–20 s to evolve [33,34]. Based on the brain energy metabolism, methods and imaging modalities, such as fNIR and fMRI [35,36] for measurements of slowly changing hemodynamic signals, deoxy-Hb and/or oxy-Hb are implemented to provide correlates of brain activity through oxygen consumption by neurons.

6.2.2 Physical Principles: How Can Hemodynamic Activity Be Measured by Optics?

It is well-known that the functional state of tissue can influence its optical properties, for instance, cyanosis in hypoxia; pallor in anemia. The human brain undergoes a number of physiological changes as it responds to environmental stimuli; these changes in blood levels and electrochemical activity also affect its optical properties. Functional optical imaging capitalizes on the changing optical properties of these tissues by using light in the near-infrared range (700–900 nm) to measure physiological changes. Because oxy-Hb and deoxy-Hb have characteristic optical properties in the visible and near-infrared light range between 700 and 900 nm, the change in concentration of these molecules during neurovascular coupling can be measured using optical methods [9,37]. Most biological tissues are relatively transparent to light in the near-infrared range, largely because major components of most tissues, such as water absorb very little energy at these wavelengths (see Figure 6.1). As such, this spectral band is often referred to as the “optical window” for the noninvasive assessment of brain activation. However,

FIGURE 6.1 Absorption spectrum in near-infrared (IR) window.

the chromophores oxy-Hb and deoxy-Hb do absorb a fair amount of energy in this range. Fortunately,in the optical window, the absorption spectra of oxy-Hb and deoxy-Hb remain significantly different than each other as shown in Figure 6.1 allowing spectroscopic separation of these compounds to be possible using only a few sample wavelengths.

Typically, an fNIR apparatus is comprised of a light source that is coupled to the participant’s head via either light-emitting diodes (LEDs) or though fiber-optical bundles (the optode), and a light detector that receives the light after it has interacted with the tissue. Photons that enter tissue undergo two different types of interaction, namely absorption and scattering [4,5,19]. When photons get absorbed by the tissue they lose their energy to the medium and hence cannot continue to travel within the tissue. After entering the tissue, photons get diffused and experience multiple scattering events. Hence, a photodetector placed 2–7 cm away from the light source can collect a relatively predictable quantity of photons that are not absorbed and traveled within the tissue along the “banana-shaped path” between the source and detector due to multiple scattering [9,38] as shown in Figure 6.2. When the distance between the source and photodetector is set at 4 cm, the fNIR signal becomes sensitive to hemodynamic changes within the top 2–3 mm of the cortex and extends laterally 1 cm to either side, perpendicular to the axis of source-detector spacing [39]. Studies have shown that at inter-optode distances as short as 2–2.5 cm,grey matter is part of the sample volume [39,40]. If wavelengths of the light sources are chosen to maximize the amount of absorption by oxy-Hb and deoxy-Hb, changes in the chromophore concentrations cause changes in the number of photons that are absorbed and the number of photons that are scattered back to the surface of the scalp. These changes in the attenuation of light measured at the surface of the scalp can be quantified using different techniques, that is, diffusion equation, modified Beer–Lambert law, and so on, and information on changes in oxy-Hb and deoxy-Hb concentrations can be assessed which will be discussed in Section 6.5.

6.3 Instrumentation

A wide variety of both commercial and custom-built fNIR instruments are currently in use [5]. These systems differ with respect to their use and system engineering, with tradeoffs between light sources, detectors, and instrument electronics that result in tradeoffs in the information available for analysis, safety, and cost. Three distinct types of fNIR implementation have been developed: time domain (TD) systems, frequency domain (FD) systems, and continuous wave (CW) spectroscopy systems, each with their own strengths and limitations [3–5]. In TD systems, also referred to as time-resolved spectroscopy (TRS), extremely short (picosecond-order) incident pulses of laser light are applied to the tissue and the temporal distribution of photons that carry the information about tissue scattering and absorption is measured. The emerging intensity is detected as a function of time (the temporal point spread function [TPSF]) with picosecond resolution [7,39,41]. Streak camera systems can provide high-temporal resolution, but they are large, expensive, and have a limited dynamic range. Time-correlated single-photon counting systems can be built with cheaper components and can provide wide dynamic range, however, they have poor temporal resolution. Even though TRS instruments offer absolute measurements of hemodynamic changes since they can be large, expensive, with limited dynamic range or poor temporal resolution, they have originally been developed as laboratory-based devices, and hence are difficult to be implemented in the clinical environment and in the field applications [5]. In FD or phase modulation spectroscopy (PM) systems, the light source is intensity modulated to the frequencies in the order of tens to hundreds of megahertz. The amplitude decay, phase shift, and modulation depth of the detected light intensity with respect to the incident light are measured to characterize the optical properties of tissue [42]. FD methods are low-cost alternatives to time-resolved methods and hence several multichannel FD instruments are now in common use [7,43].

CW systems apply either continuous or a slow-pulsed light to tissue and are limited to measuring the amplitude attenuation of the incident light [45]. These systems utilize less sophisticated detectors than time-resolved and FD systems and they cannot resolve the time-changing component of the light. As such, CW systems provide somewhat less information than time- or FD systems meaning relative measurements as opposed to absolute ones, but this tradeoff results in the capacity to design more compact, portable, easy to engineer, and affordable hardware making it advantageous for various applications [45,46]. They can be laser-based, but LEDs can also be used in CW designs to increase safety (particularly with respect to eye exposure) and comfort, and to again decrease both instrument size and cost, making it possible to deploy these systems in clinical or educational settings [5,7,32]. A detailed list of both commercially available and laboratory prototype fNIR instruments are presented in [43].

6.4 fNIR Measurements

6.4.1 Fast Neuronal Signal

Fast neuronal signal or event-related optical signal (EROS) capitalizes on the changes in the optical properties of the cell membranes themselves that occur as a function of the ionic fluxes during firing [14]. Using invasive techniques, it has been well-established that the optical properties of cell membranes change in the depolarized state relative to the resting state [32,47–49] and that optical methods can be used to detect these changes that occur within the first 200 ms of functional stimulation. The ability to measure the actual depolarization state of neuronal tissue provides obvious advantages in that it is a direct measure of neural activity, with millisecond-level time resolution as can be measured with EEG and MEG but with the superior spatial resolution lacking in EEG/MEG. However, there are also a number of limitations to the noninvasive use of the EROS signal in humans. A primary disadvantage of the fast optical signal is the low signal- to-noise ratio (SNR) resulting from the need to image through skin, skull, and cerebral-spinal fluid. Basic sensory and motor movements such as tactile stimulation and finger tapping require between 500 and 1000 trials to establish a reliable signal [13]. There have also been failures to replicate the results of experiments reporting the fast optical signal in response to a visual stimulus among normal adult humans [32]. The low SNR may play a role in current difficulties with experimental replication; however, more cross-validation work is warranted. The final constraint is that these methods require a more expensive and cumbersome laser-based light source (vs. an LED-based light source), they are not portable, and the potential risk of inadvertent damage to the eyes is increased relative to the systems available for measuring hemodynamic responses. (LED-based nearinfrared sources pose very little, if any, risk upon eye exposure [50]). In spite of these current limitations, the fast optical signal continues to be an important area of investigation because it offers glimpses of the “holy grail” of neuroimaging: the direct measurement of neuronal activity with millisecond time resolution and superior spatial resolution.

6.4.2 Slow Hemodynamic Signal

As explained in Section 6.2.1 through brain-energy metabolism, during brain activity first local oxygen consumption increases to metabolize glucose and provide energy to the activated neurons. Next, blood flow and perfusion increases in the area of activated neurons through neurovascular coupling which in turn changes the hemoglobin concentrations and oxygenation. These slow changes in hemodynamic signal occur within a few seconds after the onset of the stimulation and takes 10–20 min to take its full course to evolve [33,34] and can be measured by fNIR, PET, and fMRI as blood oxygen level dependent (BOLD) signal that is related with the changes in the concentration of deoxy-Hb.

Most fNIR applications are based upon the measurement of the slow hemodynamic responses in terms of deoxy-Hb and oxy-Hb. Typical slow hemodynamic signals together with corresponding fMRI– BOLD signal collected during a finger tapping experiment is shown in Figure 6.3a. Either the full-time course of the hemodynamic signals and/or features that can be extracted from them such as maximum amplitude, time to peak or reaction time, full width half maximum, and so on, as shown in Figure 6.3b are then used for comparison purposes in different task conditions, spatial locations or subject populations which will be discussed in detail in Sections 6.5 and 6.6.

6.5 fNIR Signal Processing

Analysis of fNIR measurements involves two main steps: (i) artifact and/or noise removal, and (ii) conversion of optical measurements into physiologically relevant signals and/or features. fNIR measurements can get corrupted by different sources of noise that should be suppressed in order to reliably extract information-bearing signals that are related to cognitive activity. Depending on the fNIR system used optical intensity measurements are converted to physiologically relevant signals and features for further processing using different approximations, assumptions, and algorithms. In this p, we will review different sources and characteristics of noise and existing algorithms to suppress them and the algorithms used to extract hemodynamic variables from fNIR intensity measurements.

6.5.1 Signal Separation and Noise Removal

The sources of noise in fNIR measurements can be categorized in two main groups: (i) noise of nonphysiological basis, and (ii) artifacts arise from systemic physiological origins. Noise sources that are not driven by physiological origins can happen as a result of instrumental noise, that is, electrical noise or experimental errors, that is, motion artifact, task-related errors. Since fNIR systems measure changes in hemodynamics, they measure such changes not only related with cognitive activity but also the ones that occur due to heart pulsation, respiration, and so on, resulting in systemic physiological artifacts. A detailed explanation of these noise sources and some algorithms for their suppression is presented in [52]. In this p, we will briefly explain these different sources of noise and summarize currently existing algorithms for their suppression.

Note that, noise in the optical measurements can be removed before and after the conversion of raw intensity measurements to physiological hemoglobin concentrations. The noise of nonphysiological basis such as instrument noise or experimental errors that are not related to underlying physiological changes should be removed prior to conversion of signals into hemodynamic measures. This way, errors across wavelengths will not be propagated causing additional crosstalk in the separation of oxy-Hb and deoxy-Hb. In contrast, noise of physiological origins such as blood pressure changes, heart pulsations, and so on, causes oscillations in hemoglobin concentrations together with changes related to brain activity such biological noise is better removed after the conversion of raw intensity measurements to hemodynamic variables [52].