**Applications of Near Infrared Spectroscopy in Neurorehabilitation**

Masahito Mihara and Ichiro Miyai *Neurorehabilitation Research Institute, Morinomiya Hospital* 

*Japan* 

## **1. Introduction**

40 Infrared Spectroscopy – Life and Biomedical Sciences

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In developed countries, stroke is a major cause of acquired disability among adults. Although there is a considerable inter-subject variability, the time course of functional recovery assumes an exponential shape, with a faster recovery in the initial few weeks, followed by a slower recovery over the next few months (Jorgensen et al., 1999; Duncan et al., 2000). In the former phase, faster recovery is thought to be due to the reduction of parenchymal oedema or recanalization of the blood flow. The latter phase is believed to depend upon the adaptive plasticity of the brain, including unmasking or disinhibiting the potentially aberrant neural network, and vicariation of function (Ward & Frackowiak, 2004). Although there are many evidences for brain plasticity after stroke or brain injury, most of our knowledge is derived from animal experiments (Jenkins & Merzenich, 1987; Nudo et al., 1996). Direct investigation of functional reorganization after brain damage in humans has only recently become possible with advancements in non-invasive functional imaging techniques, such as positron emission tomography (PET) and functional MRI (fMRI). Among these functional neuroimaging techniques, functional near infrared spectroscopy (NIRS) has drawn attention from investigators in rehabilitation medicine since it is thought to be less constrained and more available for measurement during various tasks. In this chapter, we introduce the clinical applications of fNIRS in the field of rehabilitation medicine and I shall discuss the further possibilities for its application.

### **2. Application of functional NIRS in studies of human motor control**

#### **2.1 Principles of functional NIRS**

Near infrared light, particularly that with a wavelength between 700 and 900 nm, can easily pass through biological tissues, including skin and skull bone, and be absorbed by biological chromophores such as haemoglobin, myoglobin, and cytochrome oxidase in the mitochondria. Because myoglobin concentration is much lower than haemoglobin concentrations in the brain tissue and a change in the redox state of cytochrome oxidase occurs only under severely hypoxic conditions, near infrared light is mainly absorbed by haemoglobin when used as a functional brain-imaging tool. The NIRS system with continuous waves, which is widely used in commercially available instruments, measures the transmitted intensity and calculates the relative changes in the haemoglobin concentration according to the modified Beer-Lambert law for highly scattering media

Applications of Near Infrared Spectroscopy in Neurorehabilitation 43

changes, but only relative changes, in the haemoglobin concentration. Finally, not only the brain tissue but also skin tissue beneath the optodes can affect NIRS signal changes. To avoid or cancel the effect of skin blood flow, several methodologies have been introduced (Kohno et al., 2007; Yamada et al., 2009), but there is no 'gold standard' for this problem. Therefore, researchers should be cautious about the contamination of these non-brain

Gait requires complex visuo-sensorimotor coordination. Like in other animals, human locomotion is controlled by multiple neural systems, hierarchically distributed throughout the central nervous system, including the spinal cord, brainstem, cerebellum, basal ganglia, and motor cortex (Grillner & Wallen, 2004). Although most studies of neuronal mechanisms of gait control were conducted with quadruped animals, a bipedal stance and gait are unique functions of humans. Therefore, functional imaging studies in humans are important for investigating the neural mechanisms of gait control. However, as stated above, it is difficult to study dynamic movements such as gait control with conventional neuroimaging

Using a multi-channel NIRS system, Miyai and colleagues reported cortical activation during human gait on a treadmill (Miyai et al., 2001). They used a custom-made plastic holder cap and a weight-balancing system to avoid excessive motion artifacts during the locomotor task, and they could measure the task-related haemoglobin signal changes from

A: Subject performing a locomotor task on the treadmill. B: A custom-made plastic holder cap for fixing optode fibres. C: The schematic location of each optode and channel. Cz represents the vertex. Red and

Fig. 1. Measurement of cortical activation during walking by using a functional NIRS system

In healthy subjects, the locomotor task on a treadmill evoked symmetrical activation in the medial sensorimotor cortex and supplementary motor area (Fig. 2). These findings were consistent with results from a study using single photon emission tomography (Fukuyama

signals when interpreting NIRS measurements (Takahashi et al., 2011).

techniques, and functional NIRS is a suitable tool for these studies.

**2.3.1 Cortical activation of gait in healthy subjects** 

blue circles represent the light sources and detector fibres.

the frontoparietal skull surface (Fig. 1).

**2.3 Application of NIRS to human gait control** 

(MBLL) (Cope et al., 1988). If the light attenuation by scattering is considered constant, MBLL is denoted as follows:

$$
\Delta A\_{\lambda 1} = \left( \varepsilon\_{\lambda 1}^{O \times yHb} \cdot \Delta C^{O \times yHb} + \varepsilon\_{\lambda 1}^{De \times yHb} \cdot \Delta C^{De \times yHb} \right) \cdot L
$$

Where ελ is the extinction coefficient at a given wavelength λ, L is the optical pathlength, and ∆C is the change in the concentration of each chromophore. If measurements with multiple wavelengths are performed simultaneously and optical pathlength is considered to be constant across the measurement, the product of the change in concentration of the chromophore and the optical pathlength can be calculated by solving the simultaneous equations. However, it should be noted that the precise optical pathlength is difficult to determine with the continuous-wave NIRS system. Therefore, calculated measurements are usually denoted in arbitrary units such as millimolar·millimetres (mM × mm) (Maki et al., 1995). It is generally accepted that the distribution of near infrared light paths between an illuminator-detector pair become 'banana-shaped' (Gratton et al., 1994), and that certain interoptode distances are needed for the propagation of near infrared light to the cerebral cortex. Commonly, a distance of 2 cm or more is used.

In the brain tissues, regional brain activation is accompanied by an increase in the regional blood flow (Fox & Raichle, 1986), and this regional blood flow increase is thought to exceed the regional oxygen consumption. Therefore, regional cortical activation results in a regional increase in the oxygenated haemoglobin (OxyHb) levels, with a decrease in the deoxygenated haemoglobin (DeoxyHb) levels. Similar to fMRI or PET, functional NIRS detects the task-related haemodynamic responses, that is, the task-related increase in the OxyHb signal and/or the task-related decrease in DeoxyHb.

#### **2.2 Potential advantages and shortcomings of functional NIRS**

There are several potential advantages of functional NIRS for investigating human brain activity. First, functional NIRS imposes less onerous constraints on its subjects. In a NIRS system, minor head and truncal motion is irrelevant, if a tight contact is maintained between the skull surface and optodes during measurement. Second, unlike other neuroimaging modalities, functional NIRS requires relatively small and simple equipment. Finally, the NIRS system is completely safe and non-invasive, since it uses only a low-power near infrared laser. It therefore enables us to investigate brain activation under natural conditions, such as at the bedside or while sitting on a chair, and measure cortical activation in the activities of daily life, such as standing and walking. Based on these characteristics, NIRS is thought to be a suitable neuroimaging tool for clinical investigation in fields such as paediatric neurology and rehabilitation medicine.

Despite these potential advantages, NIRS has several shortcomings as a functional neuroimaging tool. First, NIRS cannot measure activation in deep brain structures, including the basal ganglia, brainstem, and cerebellum. Secondly, NIRS has relatively poor spatial resolution (a few centimetres) and cannot provide any spatial information. Therefore, spatial registration should be made with other data, such as anatomical information from MRI scans and real-world coordinates derived from a 3-dimensional digitizer and other standard references (Okamoto et al., 2004). Third, with the continuous-wave NIRS system, we cannot measure the precise optical pathlength, and therefore cannot measure absolute

(MBLL) (Cope et al., 1988). If the light attenuation by scattering is considered constant,

Where ελ is the extinction coefficient at a given wavelength λ, L is the optical pathlength, and ∆C is the change in the concentration of each chromophore. If measurements with multiple wavelengths are performed simultaneously and optical pathlength is considered to be constant across the measurement, the product of the change in concentration of the chromophore and the optical pathlength can be calculated by solving the simultaneous equations. However, it should be noted that the precise optical pathlength is difficult to determine with the continuous-wave NIRS system. Therefore, calculated measurements are usually denoted in arbitrary units such as millimolar·millimetres (mM × mm) (Maki et al., 1995). It is generally accepted that the distribution of near infrared light paths between an illuminator-detector pair become 'banana-shaped' (Gratton et al., 1994), and that certain interoptode distances are needed for the propagation of near infrared light to the cerebral

In the brain tissues, regional brain activation is accompanied by an increase in the regional blood flow (Fox & Raichle, 1986), and this regional blood flow increase is thought to exceed the regional oxygen consumption. Therefore, regional cortical activation results in a regional increase in the oxygenated haemoglobin (OxyHb) levels, with a decrease in the deoxygenated haemoglobin (DeoxyHb) levels. Similar to fMRI or PET, functional NIRS detects the task-related haemodynamic responses, that is, the task-related increase in the

There are several potential advantages of functional NIRS for investigating human brain activity. First, functional NIRS imposes less onerous constraints on its subjects. In a NIRS system, minor head and truncal motion is irrelevant, if a tight contact is maintained between the skull surface and optodes during measurement. Second, unlike other neuroimaging modalities, functional NIRS requires relatively small and simple equipment. Finally, the NIRS system is completely safe and non-invasive, since it uses only a low-power near infrared laser. It therefore enables us to investigate brain activation under natural conditions, such as at the bedside or while sitting on a chair, and measure cortical activation in the activities of daily life, such as standing and walking. Based on these characteristics, NIRS is thought to be a suitable neuroimaging tool for clinical investigation in fields such as

Despite these potential advantages, NIRS has several shortcomings as a functional neuroimaging tool. First, NIRS cannot measure activation in deep brain structures, including the basal ganglia, brainstem, and cerebellum. Secondly, NIRS has relatively poor spatial resolution (a few centimetres) and cannot provide any spatial information. Therefore, spatial registration should be made with other data, such as anatomical information from MRI scans and real-world coordinates derived from a 3-dimensional digitizer and other standard references (Okamoto et al., 2004). Third, with the continuous-wave NIRS system, we cannot measure the precise optical pathlength, and therefore cannot measure absolute

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MBLL is denoted as follows:

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cortex. Commonly, a distance of 2 cm or more is used.

OxyHb signal and/or the task-related decrease in DeoxyHb.

paediatric neurology and rehabilitation medicine.

**2.2 Potential advantages and shortcomings of functional NIRS** 

changes, but only relative changes, in the haemoglobin concentration. Finally, not only the brain tissue but also skin tissue beneath the optodes can affect NIRS signal changes. To avoid or cancel the effect of skin blood flow, several methodologies have been introduced (Kohno et al., 2007; Yamada et al., 2009), but there is no 'gold standard' for this problem. Therefore, researchers should be cautious about the contamination of these non-brain signals when interpreting NIRS measurements (Takahashi et al., 2011).
