Date Published: June 22, 2015
Publisher: Springer New York
Author(s): David Highton, Ilias Tachtsidis, Alison Tucker, Clare Elwell, Martin Smith.
Acute brain injury (ABI) is associated with changes in near infrared light absorption reflecting haemodynamic and metabolic status via changes in cerebral oxygenation (haemoglobin oxygenation and cytochrome-c-oxidase oxidation). Light scattering has not been comprehensively investigated following ABI and may be an important confounding factor in the assessment of chromophore concentration changes, and/or a novel non-invasive optical marker of brain tissue morphology, cytostructure, hence metabolic status. The aim of this study is to characterize light scattering following adult ABI. Time resolved spectroscopy was performed as a component of multimodal neuromonitoring in critically ill brain injured patients. The scattering coefficient (μ′s), absorption coefficient and cerebral haemoglobin oxygen saturation (SO2) were derived by fitting the time resolved data. Cerebral infarction was subsequently defined on routine clinical imaging. In total, 21 patients with ABI were studied. Ten patients suffered a unilateral frontal infarction, and mean μ′s was lower over infarcted compared to non-infarcted cortex (injured 6.9/cm, non-injured 8.2/cm p = 0.002). SO2 did not differ significantly between the two sides (injured 69.3 %, non-injured 69.0 % p = 0.7). Cerebral infarction is associated with changes in μ′s which might be a novel marker of cerebral injury and will interfere with quantification of haemoglobin/cytochrome c oxidase concentration. Although further work combining optical and physiological analysis is required to elucidate the significance of these results, μ′s may be uniquely placed as a non-invasive biomarker of cerebral energy failure as well as gross tissue changes.
The optical characteristics of cerebral tissues following acute brain brain injury (ABI) have been of considerable clinical interest, because they can be exploited to interrogate cerebral oxygenation in-vivo, non-invasively. An optical window in the near infrared spectrum (700–900 nm) facilitates measurement of the dominant absorbing chromophores in this region—oxy/deoxy-haemoglobin and cytochrome c oxidase, by their relative specific absorption spectra—thus inferring information about the haemodynamic and metabolic status of the brain . However light transport through complex biological media is highly dependent on light scattering as well as absorption, which has not been comprehensively investigated following ABI, and may be an important confounding factor in the assessment of chromophore concentration changes , and/or a novel non-invasive optical marker of brain tissue morphology, cytostructure, hence metabolic status . The aim of this study is to characterize light scattering in brain tissue following adult ABI.
A total of 21 critically ill, ventilated brain injured patients were recruited following ethical approval and representative consent. Time resolved spectroscopy (TRS-20, Hamamatsu Photonics KK) was performed as a component of multimodal neuromonitoring in critically ill brain injured patients. Serial recordings were taken whilst in critical care. The reduced scattering scattering coefficient (μ′s), absorption coefficient, cerebral haemoglobin oxygen saturation (SO2) and total haemoglobin concentration ([HbT]) were derived by fitting the time resolved data (diffusion equation for light transport in a semi-infinite homogeneous medium, fitting the entire temporal point spread function, as standard within the Hamamatsu software). Three bilateral time-resolved recordings were made over frontal cortex at 4 cm source detector separation with a 5 s acquisition time. The mean of these three recordings were used for comparison. Cerebral infarction was subsequently defined on routine clinical imaging and paired comparison of μ′s was performed in patients with unilateral infarction, using the paired t-test. μ′s
Patients’ characteristics are summarised in Table 17.1 and the μ′s and SO2 data are summarised in Fig. 17.1. Ten patients suffered a unilateral frontal infarction, and mean μ′s was lower over infarcted compared to non-infarcted cortex (Table 17.2). SO2 (injured 69.3 %, non-injured 69.0 % p = 0.7) and [HbT] (injured 64.6 μmol−1, non-injured 51.9 μmol−1 p = 0.09) did not differ significantly. The time course of μ′s data is shown in Fig. 17.1 suggesting a trend of increasing μ′s with respect to time in the infarct group:- however the patient group is heterogeneous, as is the onset of infarction.Table 17.1Patient characteristics. Reported as median [quartile] or number (percentage)Age (years)58 [47, 70]Diagnosis Subarachnoid haemorrhage (%)11 (52) Intracerebral haemorrhage (%)8 (38) Ischaemic stroke (%)1 (5) Traumatic brain brain injury (%)1 (5)In-hospital mortality (%)4 (19)Fig. 17.1Mean μ′s (834 nm) and SO2 for each day post intensive care admission in cerebral hemispheres demonstrating infarction versus no infarction. The lower scattering in infarcted cerebral hemisphere is evident, whereas there is no appreciable pattern with SO2Table 17.2μ′s measured over infarcted and non-infarcted cortexμ′s761 nm (cm−1)μ′s801 nm (cm−1)μ′s834 nm (cm−1)Infarct7.43 (1.74)7.18 (1.64)6.87 (1.57)No infarct8.84 (1.51)8.52 (1.45)8.20 (1.43)p-value0.0030.0030.002Brackets denote standard deviation
Cerebral infarction is associated with significant reduction in μ′s below previously reported values for normal adults . Unilateral infarction was not associated with a similar difference in SO2 or [HbT] indicating either less discriminatory ability of these complex physiological variables or error in the assumptions underlying their derivation. The wavelength dependence of μ′s was approximately linear over the narrow band of wavelengths studied and revealed similar parameter estimates to other reports of cerebral tissues in vivo  and in vitro . This did not vary between injured and non-injured cortex. Clearly these findings have potentially important implications for analysis using differential spectroscopy over injured brain as variation in μ′s violates assumptions required to calculate concentration changes.