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

Abstract

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.

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

“…Assuming that the concentration of red blood cells (hematocrit level) remains constant following injury, THC can be used as a surrogate marker of CBF. Reduced CBF following brain trauma observed here is consistent with our previous studies 34,35 and stands in agreement with results of neuroimaging studies, which revealed heterogeneous regional disturbances of CBF. [50][51][52] Under decreased CBF, brain cells undergo a series of pathophysiologic changes further complicated by decreased oxygen supply, as reflected in lowered StO 2 , contributing to secondary injury.…”

“…Thus, it appears that morphine was able to delay or prevent the gradual decrease of sp seen in untreated TBI. 34,35 This delay in cell swelling, probably reflecting a decrease in ICP, is in agreement with Lauer et al, who reported that morphine administration preserves systemic arterial pressure without elevating ICP in head injury patients. 63 It should be stressed that the clinical effectiveness of morphine for the reduction of ICP in severe head injury remains open to question.…”

“…At the same time, in comparison to our previous studies using the same animal TBI model and optical setup (Ref. 34, Fig. 3 and Ref.…”

“…This figure also demonstrates our ability to follow changes over time in order to monitor cellular swelling within brain structure in high time resolution [Ref. 34,Fig. 7].…”

“…Our earlier works with different optical platforms showed evidence of morphological and physiological impairments in a mouse model of focal TBI. 34,35 However, the effects of neuroprotective drugs for mitigating brain damage associated with TBI was not investigated previously using DRS. The long-term goal of the present research is to perform extensive investigation of a wide range of clinical drugs to identify the most efficient neuroprotective drug treatment strategy for brain injury patients.…”