Noninvasive early detection of brain edema in mice by near-infrared light scattering

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Abstract
Brain edema accounts for significant morbidity and mortality in many neurologic conditions such as head trauma, stroke, meningitis, and brain tumor. The water channel aquaporin‐4 (AQP4) has been found to be an important determinant of brain water accumulation and clearance of excess brain water. We report the development of a noninvasive near‐infrared (NIR) light‐scattering method to compare the early kinetics of brain swelling in normal and AQP4‐deficient mice. Brain tissue was illuminated through the intact skull with NIR light at 850 nm, and steady‐state scattered light intensity was monitored at an angle of 90 degrees at a position on the skull ∼10 mm from the illuminated site. NIR light scattering reversibly increased with brain swelling (ΔI/Io ∼25% per 1% increase in brain water content), but was insensitive to changes in cerebral blood flow, blood oxygenation, or blood flow‐related changes in intracranial pressure (ICP). ΔI/Io increased approximately linearly with brain water content as measured by wet‐to‐dry weight ratios. Acute water intoxication (intraperitoneal water, 20% body weight) produced a gradual increase in ΔI/Io of 12 ± 4% in wild‐type mice at 5 min, much greater than that of 2 ± 1% in AQP4‐null mice. Correlation of the NIR signal with ICP showed that increased ΔI/Io preceded measurable increases in ICP, indicating the ability of the NIR method to detect early brain edema before ICP elevation. NIR light scattering provides a simple noninvasive method to monitor brain edema in mice, with potential clinical applications.

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