Noninvasive assessment of hemodynamic and brain metabolism parameters following closed head injury in a mouse model by comparative diffuse optical reflectance approaches.

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.

Differential effects of early postinjury treatment with neuroprotective drugs in a mouse model using diffuse reflectance spectroscopy.

The time required for the arrival of an ambulance crew and administration of first aid is critical to clinical outcome, particularly in the case of head injury victims requiring neuroprotective drugs following a car accident, falls, and assaults. Short response times of the medical team, together with proper treatment, can limit injury severity and even save a life before transportation to the nearest medical center. We present a comparative evaluation of five different neuroprotective drugs frequently used in intensive care and operating units in the early phase following traumatic brain injury (TBI): hypertonic saline (HTS), mannitol, morphine, melatonin, and minocycline. The effectiveness of these drugs in terms of changes in brain tissue morphology (cell organelle size, density, distribution, etc.) and biochemical tissue properties (chromophores' content) was experimentally evaluated through analysis of the spectral reduced scattering and optical absorption coefficient parameters in the near-infrared (NIR) optical range (650 to 1000 nm). Experiments were conducted on anesthetized male mice subjected to a noninvasive closed head weight-drop model of focal TBI ([Formula: see text] and [Formula: see text] control) and monitored using an NIR diffuse reflectance spectroscopy system utilizing independent source-detector separation and location. After 10 min of baseline measurement, focal TBI was induced and measurements were conducted for 20 min. Subsequently, a neuroprotective drug was administrated and measurements were recorded for another 30 min. This work's major findings are threefold: first, minocycline was found to improve hemodynamic outcome at the earliest time postinjury. Second, HTS decreased brain water content and inhibited the increase in intracranial pressure. Third, the efficacy of neuroprotective drugs can be monitored noninvasively with diffuse reflectance spectroscopy. The demonstrated ability to noninvasively detect cerebral physiological properties following early administration of neuroprotective drugs underlines the need for more extensive investigation of the combined use of clinical drugs in larger-scale preclinical experiments to find the most beneficial drug treatment for brain injury patients.

Exploring diazepam's effect on hemodynamic responses of mouse brain tissue by optical spectroscopic imaging.

In this study, a simple duel-optical spectroscopic imaging apparatus capable of simultaneously determining relative changes in brain oxy-and deoxy-hemoglobin concentrations was used following administration of the anxiolytic compound diazepam in mice with strong dominant (Dom) and submissive (Sub) behavioral traits. Three month old mice (n = 30) were anesthetized and after 10 min of baseline imaging, diazepam (1.5 mg/kg) was administered and measurements were taken for 80 min. The mouse head was illuminated by white light based LED's and diffused reflected light passing through different channels, consisting of a bandpass filter and a CCD camera, respectively, was collected and analyzed to measure the hemodynamic response. This work's major findings are threefold: first, Dom and Sub animals showed statistically significant differences in hemodynamic response to diazepam administration. Secondly, diazepam was found to more strongly affect the Sub group. Thirdly, different time-series profiles were observed post-injection, which can serve as a possible marker for the groups' differentiation. To the best of our knowledge, this is the first report on the effects of an anxiolytic drug on brain hemodynamic responses in mice using diffused light optical imaging.

Monitoring hemodynamic and morphologic responses to closed head injury in a mouse model using orthogonal diffuse near-infrared light reflectance spectroscopy.

The authors' aim is to assess and quantitatively measure brain hemodynamic and morphological variations during closed-head injury (CHI) in mice using orthogonal diffuse near-infrared reflectance spectroscopy (o-DRS). CHI is a type of injury to the head that does not penetrate the skull. Usually, it is caused by mechanical blows to the head and frequently occurs in traffic accidents, falls, and assaults. Measurements of brain optical properties, namely absorption and reduced scattering coefficients in the wavelength range from 650 to 1000 nm were carried out by employing different source-detector distance and locations to provide depth sensitivity on an intact scalp over the duration of the whole experiment. Furthermore, alteration in both cortical hemodynamics and morphologic markers, i.e., scattering power and amplitude properties were derived. CHI was induced in anesthetized male mice by a weight-drop model using ∼50 g cylindrical metal falling from a height of 90 cm onto the intact scalp producing an impact of 4500 g cm. With respect to baseline, difference in brain physiological properties was observed following injury up to 1 h post-trauma. Additionally, the reduced scattering spectral shapes followed Mie scattering theory was quantified and clearly shows changes in both scattering amplitude and power from baseline indicating structural variations likely from evolving cerebral edema during CHI. We further demonstrate high correlation between scattering amplitude and scattering power, with more than 20% difference in slope in comparison to preinjury. This result indicates the possibility of using the slope also as a marker for detection of structural changes. Finally, experiments investigating brain function during the first 20 min postinjury were conducted and changes in chromophore concentrations and scattering were observed. Overall, our experiments demonstrate the potential of using the proposed technique as a valuable quantitative noninvasive tool for monitoring brain physiology following CHI injury at the bedside and/or at the field.