## 3 Optical Imaging Modalities to Develop and Verify Diagnosis/Treatment Techniques of Stroke
### Functional Near-Infrared Spectroscopy  
Both ischemic and hemorrhagic strokes are diseases caused by changes and abnormalities in a distribution of blood in cerebral blood vessels. Therefore, methods to extract information on cerebral blood flows and hemoglobin distributions in cerebral blood vessels, for instance, Doppler ultrasound imaging and vascular magnetic resonance imaging (MRI), can be employed as a noninvasive diagnostic method for stroke. The optical imaging technology, defined as a functional near-infrared spectroscopy (\(f\)NIRS), provides an ability to obtain distribution information of oxy-/deoxy-hemoglobin and total blood concentrations using infrared light sources [57; 58; 59; 60]. \(f\)NIRS does not use specific indicators, unlike fluorescence imaging. Therefore, it has been applied to preclinical tests as well as to brain function analysis and a verification of stroke rehabilitation at a clinical stage. [PERSON] et al. investigated a diffuse optical oxy-/total hemoglobin monitoring system using infrared light sources with two peak wavelengths of 785 nm and 854 nm [61]. The system, which consists of two light sources and detectors, can measure hemoglobin concentrations and blood flows in left and right sides of a mouse brain. Moreover, it demonstrated high correlation in a comparative study using a laser Doppler flowmeter and a mouse model with repeated ischemia. [PERSON] et al. applied \(f\)NIRS to confirm cerebral hemodynamic responses derived using transcranial electrical stimulation, which is one of the neurostimulation-based therapeutic techniques for brain diseases including stroke [62]. Two light sources with central wavelengths of 690 nm and 830 nm, and detectors associated with fiber-optic probes, were installed in left and right sides of a rat brain. Further, hemodynamic responses were measured for direct current simulation by an electrode, which was placed between the fiber-optic probes of the light sources and the detector. [PERSON] et al. applied an infrared diffusion tomography to establish three-dimensional hemodynamic changes to a rat model that performed ischemic stroke (derived by middle cerebral artery to create a permanent occlusion (MCAO)) and its treatment (reperfusion), as illustrated in Figure 3b [63]. _f_NIRS is also applied to a diagnosis of stroke and to monitoring an effectiveness of rehabilitation and treatment in cerebrovascular stroke patients in a clinical stage. [PERSON] et al. conducted a pilot study of_f_NIRS to detect acute ischemic stroke and a good responsiveness in stroke-derived changes was confirmed in a small clinical research study [64]. [PERSON] et al. studied a diagnostic feature extraction of acute ischemic stroke for oxy-/deoxy-/total hemoglobin and tissue oxygen saturation that can be measured by _f_NIRS (with detailed probe distribution described in Figure 3c) in a clinical stage [65]. Several research groups analyzed a validity and performance of rehabilitation applications and gait training for stroke through a noninvasive observation of cortical activations using _f_NIRS [66, 67, 68, 69, 70]. [PERSON] et al. studied typical cortical activations during a cycle rehabilitation exercise of stroke patients [71]. The study found that despite the existing differences in a degree of activation, both passive and active cycle rehabilitation exercises contribute to premotor cortex activations. Studies using_f_NIRS as a clinical validation tool for stroke treatments based on various physical stimulations are also being conducted extensively. [PERSON] et al. measured electroencephalographic signals and oxy-hemoglobin during transcranial direct current electrostimulation therapies in stroke patients using a multimodal neuro-signal measurements probe linked to electroencephalography (EEG) and _f_NIRS [72, 73].