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Optical techniques have gained substantial interest over the past four decades for biomedical imaging due to their unique advantages, which may suggest their use as alternatives to conventional methodologies. Several optical techniques have been successfully adapted to clinical practice and biomedical research to monitor tissue structure and function in both humans and animal models. This paper reviews the analysis of the optical properties of brain tissue in the wavelength range between 500 and 1000 nm by three different diffuse optical reflectance methods: spatially modulated illumination, orthogonal diffuse light spectroscopy, and dual-wavelength laser speckle imaging, to monitor changes in brain tissue morphology, chromophore content, and metabolism following head injury. After induction of closed head injury upon anesthetized mice by weight-drop method, significant changes in hemoglobin oxygen saturation, blood flow, and metabolism were readily detectible by all three optical setups, up to 1 h post-trauma. Furthermore, the experimental results clearly demonstrate the feasibility and reliability of the three methodologies, and the differences between the system performances and capabilities are also discussed. The long-term goal of this line of study is to combine these optical systems to study brain pathophysiology in high spatiotemporal resolution using additional models of brain trauma. Such combined use of complementary algorithms should fill the gaps in each system's capabilities, toward the development of a noninvasive, quantitative tool to expand our knowledge of the principles underlying brain function following trauma, and to monitor the efficacy of therapeutic interventions in the clinic.

Abstract. The measurement of dynamic changes in brain hemodynamic and metabolism events following head trauma could be valuable for injury prognosis and for planning of optimal medical treatment. Specifically, variations in blood flow and oxygenation levels serve as important biomarkers of numerous pathophysiological processes. We employed the dual-wavelength laser speckle imaging (DW-LSI) technique for simultaneous monitoring of changes in brain hemodynamics and cerebral blood flow (CBF) at early stages of head trauma in a mouse model of intact head injury (n=10). For induction of head injury, we used a weight-drop device involving a metal mass (∼50  g ) striking the mouse’s head in a regulated manner from a height of ∼90  cm. In comparison to baseline measurements, noticeable dynamic variations were revealed immediately and up to 1 h postinjury, which indicate the severity of brain damage and highlight the ability of the DW-LSI arrangement to track brain pathophysiology induced by injury. To validate the monitoring of CBF by DW-LSI, measurements with laser Doppler flowmetry (LDF) were also performed (n=5), which confirmed reduction in CBF following injury. A secondary focus of the study was to investigate the effectiveness of hypertonic saline as a neuroprotective agent, inhibiting the development of complications after brain injury in a subgroup of injured mice (n=5), further demonstrating the ability of DW-LSI to monitor the effects upon brain dynamics of drug treatment. Overall, our findings further support the use of DW-LSI as a noninvasive, cost-effective tool to assess changes in hemodynamics under a variety of pathological conditions, suggesting its potential contribution to the biomedical field. To the best of our knowledge, this work is the first to make use of the DW-LSI modality in a small animal model to (1) investigate brain function during the critical first hour of closed head injury trauma, (2) correlate between injury parameters of LDF measurements, and (3) monitor brain hemodynamic and metabolic response to neuroprotective drug treatment.