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Figure 1.

Generation and characteristics of laser-induced shock wave (LISW).

(A) Setup for generating an LISW. (B) Typical temporal waveforms of LISWs generated at different laser fluences on the laser target. (C) Dependences of peak pressure and impulse of LISW on laser fluence.

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Figure 2.

Measurements of diffuse reflectance signals, EEG and systemic physiological parameters for the rat whose brain was exposed to an LISW.

(A) Photograph of setup and (B) schematic of sensor positions for measurements of diffuse reflectance signals and EEG for the brain. (C) Photograph showing sensor positions for pulse oximeter and blood pressure meter. (D) Positions of fiber pairs (ch1, ch2 and ch3) and LISW application for multichannel diffuse reflectance measurement of the brain.

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Figure 3.

Results of measurements of systemic physiological parameters, EEG and diffuse reflectance signals for the brain.

Sensor positions for systemic physiological parameters (A–C), EEG (E) and diffuse reflectance signals (D, F–H) are shown in Fig. 2. A single pulse of LISW generated at 1.0 J/cm2 (φ4 mm; ∼86 MPa; ∼14 Pa•s) was applied to the brain at time zero. (A) Arterial oxygen saturation (SpO2). (B) Arterial blood pressure. (C) Heart rate. (D) Light scattering signal (diffuse reflectance signal at 805 nm, R805) indicating cellular and subcellular morphological changes. (E) EEG. The horizontal arrow indicates the duration of EEG suppression. (F) Total hemoglobin indicating regional cerebral blood volume (rCBV) (R569). The vertical dashed line indicates the turning point from hyperemia to oligemia. (G) Hemoglobin oxygenation (R578/R569). The vertical dashed line indicates the turning point from hyperoxemia to hypoxemia. The horizontal arrow indicates long-lasting hypoxemia. (H) Diffuse reflectance signal indicating reduction of heme aa3, a redox center of cytochrome c oxidase (R620/R605). The horizontal arrow indicates the duration of heme aa3 reduction.

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Table 1.

Summary of observations by measurements of diffuse reflectance signal and EEG; mark (X) indicates observed.

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Figure 4.

Results of measurements of DC potential and light scattering signal based on CCD imaging.

A single pulse of LISW generated at 1.0/cm2 (φ4 mm; ∼86 MPa; ∼14 Pa•s) was applied to the brain at time zero. (A) DC potential measured at the same position for EEG measurement (Fig. 2B). (B) Light scattering intensity in the ROI adjacent to the site of DC potential measurement.

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Figure 5.

NIR difference reflectance images (video clips) showing propagation of light scattering waves on the rat brain that was exposed to an LISW.

Images were acquired with a CCD camera under illumination with a bandpass-filtered tungsten lamp (800±70 nm). The laser target was quickly removed after laser exposure. The LISW was applied at time zero. (A) A 4-mm-diameter LISW generated at 1.0 J/cm2 (∼86 MPa; ∼14 Pa•s) was applied to the same location as that for diffuse reflectance measurement (left-most photograph and figure). (B) An 8-mm-diameter LISW generated at 0.7 J/cm2 (∼85 MPa; ∼19 Pa•s) was applied to the area around the center of the skull (left-most photograph and figure). In both (A) and (B), arrowheads indicate the front of a bright region(s), which was (were) followed by a dark region(s). Times shown in the NIR difference reflectance images indicate times after LISW application. Propagation speeds in (A) and (B) were 2.4 mm/min and 2.0 mm/min, respectively.

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Figure 6.

Stereomicroscopic observation of blood vessels in the surface of the brain that was exposed to an LISW.

The image was taken through a cranial window of 4-mm-thick PET sheet was fitted. A 4-mm-diameter LISW generated at 1.25 J/cm2 (∼104 MPa; ∼19 Pa•s) was applied to the right hand side of the window at time zero. (A) Before LISW application. (B–D) After LISW application: (B) t = 2.5 min, (C) t = 4 min and (D) t = 48 min. Diameters of some pial arteries were smaller than those before LISW application (arrowheads). Tissue color in (C) and (D) was pale. In (D), even some veins showed vasoconstriction (arrows). Some small-diameter vessels seen in (C) (asterisks) were not able to be seen clearly in (D). The state shown in (B) and states shown in (C) and (D) correspond to hyperemia/hyperoxemia and oligemia/hypoxemia, respectively, which were shown by spectroscopic diffuse reflectance measurement (Fig. 3G, F).

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Figure 7.

Results of multichannel fiber measurement of hemoglobin oxygenation level.

Positions of the fiber pair and LISW application are shown Fig. 2D. An LISW generated at 1.25 J/cm2 (φ4 mm; ∼104 MPa; ∼19 Pa•s) was applied to the frontal bone at time zero. Time courses of hemoglobin oxygenation (R578/R569) measured at (A) ch1, (B) ch2 and (C) ch3. The vertical dashed lines indicate turning points from hyperoxemia to hypoxemia.

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Figure 8.

Results of quantification of hemoglobin oxygen saturation (StO2) based on inverse Monte Carlo simulation.

To exclude uncertainty associated with optical properties of the skull, a small window was made in the skull for fiber measurement. Relative location of LISW application (φ4 mm; ∼86 MPa; ∼14 Pa•s) and the fiber pair was the same as that for diffuse reflectance measurement (Fig. 2B). Time courses of (A) StO2 and other important parameters for simulation: (B) concentrations of oxygenated hemoglobin CHbO, deoxygenated hemoglobin CHbR and total hemoglobin CTHb and (C) scattering amplitude a.

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