- Email: [email protected]
Brain tissue oxygen evaluation by wireless near-infrared spectroscopy
j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 5 ) 1 e7
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Brain tissue oxygen evaluation by wireless near-infrared spectroscopy Che-Chuan Wang, MD,a,b,c,d Jinn-Rung Kuo, MD, PhD,b,c,e Yu-Chih Chen, BS,f Chung-Ching Chio, MD,c Jhi-Joung Wang, MD, PhD,b and Bor-Shyh Lin, PhDb,f,* a
Institute of Photonic System, National Chiao-Tung University, Tainan, Taiwan Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan c Division of Neurosurgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan d Department of Child Care, Southern Taiwan University of Science and Technology, Tainan, Taiwan e Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan f Institute of Imaging and Biomedical Photonics, National Chiao-Tung University, Tainan, Taiwan b
article info
abstract
Article history:
Background: Monitoring the partial pressure of oxygen in brain tissue (PbtO2) is an impor-
Received 12 May 2015
tant tool for traumatic brain injury (TBI) but is invasive and inconvenient for real time
Received in revised form
monitoring. Near-infrared spectroscopy (NIRS), which can monitor hemoglobin parameters
14 September 2015
in the brain tissue, has been used widely as a noninvasive tool for assessing cerebral
Accepted 2 October 2015
ischemia and hypoxia. Therefore, it may have the potential as a noninvasive tool for
Available online xxx
estimating the change of PbtO2. In this study, a novel wireless NIRS system was designed to monitor hemoglobin parameters of rat brains under different impact strengths and was
Keywords:
used to estimate the change of PbtO2 noninvasively in TBI.
Traumatic brain injury
Materials and methods: The proposed wireless NIRS system and a PbtO2 monitoring system
Partial pressure of oxygen in brain
were used to monitor the oxygenation of rat brains under different impact strengths. Rats
tissue
were randomly assigned to four different impact strength groups (sham, 1.6 atm, 2.0 atm,
Near-infrared spectroscopy
and 2.4 atm; n ¼ 6 per group), and the relationships of concentration changes in oxyhe-
Oxyhemoglobin
moglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (HbT), and PbtO2 during
Deoxyhemoglobin
and after TBI with different impact strengths were investigated. Triphenyltetrazolium chloride (TTC) staining was also used to evaluate infarction volume. Results: Concentration changes in HbO2, HbR, and HbT dropped immediately after the impact, increased gradually, and then became stable. Changes in PbtO2 had a similar tendency with the hemoglobin parameters. There was significant correlation between changes in PbtO2 and HbO2 (correlation ¼ 0.76) but not with changes in HbR (correlation ¼ 0.06). In triphenyltetrazolium chloride staining, the infarction volume was highly but negatively associated with oxygen-related parameters like PbtO2 and HbO2. Conclusions: Changes in HbO2 under TBI was highly and positively correlated with changes in PbtO2. By using the relative changes in HbO2 as a reference parameter, the proposed
* Corresponding author. Institute of Imaging and Biomedical Photonics, National Chiao-Tung University, No.301, Gaofa 3rd Rd., Guiren Dist., Tainan City 711, Taiwan. Tel.: þ886 9 10181308; fax: þ886 6 2828928. E-mail address: [email protected] (B.-S. Lin). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2015.10.005
2
j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 5 ) 1 e7
wireless NIRS system may be developed as a noninvasive tool for estimating the change of PbtO2 in brain tissue after TBI. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
The partial pressure of oxygen in brain tissue (PbtO2) is usually used to evaluate the cerebral oxygenation of patients after traumatic brain injury (TBI), because the oxygenation of the injured tissue has a significant influence on recovery and outcome. Therefore, monitoring PbtO2 is an important tool for TBI patients clinically. However, PbtO2 monitoring is an invasive approach and may increase the risk of brain hemorrhage and infection. It is also inconvenient for real time monitoring. Recently, near-infrared spectroscopy (NIRS) was proposed by Jobsis in 1977 [1]. The method of near-infrared spectroscopy has been well established in neonatal care [2], carotid [3], and cardiac surgery [4]. NIRS has been used as a noninvasive real-time measurement of cerebral ischemia and hypoxia [5e8] and is also widely used in neuroscience for mapping the cerebral situation and assessing postinjury cognitive functions [9]. NIR light (700e1000 nm) penetrates skin, subcutaneous fat, and underlying muscle and is either absorbed (by oxyhemoglobin and deoxyhemoglobin) or scattered within the tissue [10]. Both the NIRS system and the PbtO2 monitoring system are used to assess physiological parameters related to the oxygen status of the brain. The measuring value of the PbtO2 monitoring system can directly reflect the status of tissue oxygen in the brain [11]. The parameters obtained by the NIRS system are related to the relative concentration of hemoglobin, such as oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (HbT), in brain tissue. Therefore, the relative concentrations of HbO2 and HbR can be related to the status of tissue oxygen. The hypothesis of this study is that the change of NIRS parameters may be highly correlated to the change of PbtO2. In this study, a wireless NIRS system was designed and implemented to monitor the changes of relative concentrations of HbO2, HbR, and HbT during and after TBI. The relationships of the concentration changes of HbO2 and HbR, and PbtO2 during and after TBI were also investigated. The relationship between hemoglobin parameters and PbtO2 under different impact strengths proves that the technique of NIRS has the potential as a noninvasive tool for estimating the change of PbtO2.
2.
Materials and methods
2.1.
Animal preparation
Twenty-four adult male SpragueeDawley rats weighing 325e375 g were fostered under a 12-h light and/or dark cycle and allowed to ad libitum access to water and food. All the experimental procedures conformed to the guidelines of the National Institute of Health, Taiwan, and were approved by the Animal Care and Use Committee of Chi-Mei Medical Center.
All the rats were randomly divided to four different impact groups (sham, 1.6 atm, 2.0 atm, and 2.4 atm) in the fluid percussion injury experiments and monitored by the NIRS system and the PbtO2 monitoring system (OxyLite 2000, Oxford Optronix). The rats were anesthetized with a sodium pentothal (25 mg/kg, i.p.; Sigma Chemical Co, St. Louis, MO) and a mixture containing ketamine (44 mg/kg, i.m.; Nan Kuang Pharmaceutical, Tainan, Taiwan), atropine (0.02633 mg/kg, i.m.; Sintong Chemical Industrial Co, Ltd, Taoyuan, Taiwan), and xylazine (6.77 mg/kg, i.m.; Bayer, Leverkusen, Germany) before the experiment. The rats were sacrificed on the third day after surgery.
2.2.
Experiment design for traumatic brain injury
The fluid percussion injury (FPI) experimental model was used as the TBI model of the rats [12]. Before the experiment, the rat was anesthetized, and the head was tied with ear bars inserted in a stereotaxic frame. To hold the rat core temperature at 37 C, a rectal temperature probe was set into the rat’s colon, and the rat was placed on a heating pad that was controlled by the thermostatic controller. The fur on the rat head was then shaved and its scalp incised sagittally. A circular hole was located and drilled on the skull to situate the impact point at 3 mm anterior-posterior and þ4 mm lateral to the bregma. A luer-lock connector was connected to a sealed and fluid-filled reservoir and fixed into the craniotomy with cyano-acrylic adhesive and dental acrylic. The monitoring systems (wireless NIRS system [13] and OxyLite 2000) were set up, including the positions of the optical measuring probe of the wireless NIRS system, the PbtO2 barefiber sensor, and the luer-lock connector. The PbtO2 bare-fiber sensor was placed nearby the luer lock and was inserted to the striatum region under stereotactic frame. The photodiode and light-emitting diode were set up at 8 mm away from the drill hole of the PbtO2 sensor (Fig. 1). Before the experiment, the relative concentrations of HbO2, HbR, and PbtO2 were monitored continuously for 30 min until the rat became stable.
Fig. 1 e Illustration for locations of luer-lock connector, near-infrared spectroscopy optical measuring probe, and partial pressure of oxygen in brain tissue bare-fiber sensor on rat skull. (Color version of figure is available online.)
j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 5 ) 1 e7
3
Baseline data were set by the 5-min raw data before the FPI experiment. A fluid wave was then generated to impact the rat brain like a pendulum that struck the reservoir. After FPI, the tongue of rats would be pulled out immediately to help the rat breathing (respiratory treatment). During the whole experimental procedure, these monitoring systems recorded continuously for 2 h. At the end of the experiment, the connector and acrylic were removed from the rat head, and the incisions on the rat were sutured.
2.3.
Cerebral infarction assay
In this study, the brain injury area was analyzed by triphenyltetrazolium chloride staining [14]. All the rats were sacrificed at 72 h after TBI. The brains of the TBI rats were taken for staining, and the infarction volume was measured by using the computerized planimetry (PC-based Image Tools software). The infarction volume was expressed as [the thickness of each slice (2 mm)] [the sum of the infarction region in all of the slices (mm2)].
2.4.
Statistical analysis
The time courses data of HbO2, HbR, and PbtO2 and the infarction volume in different groups were analyzed by analysis of variance. Statistical significance was set at P < 0.05. The linear correlation coefficients between PbtO2 and HbO2 and between PbtO2 and HbR were analyzed using MATLAB (MathWorks, Natick, MA).
3.
Results
With different impact strengths, the time courses of the relative concentration changes of HbO2, HbR, and HbT revealed that these all dropped immediately after the impact point (Fig. 2Ae2C). After applying a respiratory treatment, the relative concentration changes of HbO2, HbR, and HbT increased gradually and then became stable. The lower impact strength caused a higher increasing tendency of these parameters. Moreover, all these changes rose higher after TBI compared to their baseline values, except for the change in HbO2 under the impact strength of 2.4 atm. The time courses of changes in PbtO2 corresponding to different impact strengths demonstrated that the change of PbtO2 dropped immediately at the impact point in all the impact strengths (Fig. 3). This change tendency was similar to the tendencies of the NIRS parameters. In the 1.6 atm group, the change in PbtO2 reverted to near baseline level within 10 min (after respiratory treatment). In the 2.0 atm group, the change in PbtO2 was back near the baseline level later, but in the group of 2.4 atm, the change in PbtO2 remained in the lower levels even after 2 h. In addition, the result of correlation between changes in PbtO2 and in HbO2 (Fig. 4A) and the correlation between changes in PbtO2 and in HbR (Fig. 4B) revealed that the change in PbtO2 significant correlated with the change in HbO2 (correlation coefficient ¼ 0.76) but not with the change in HbR (correlation coefficient ¼ 0.06). The correlation between the change of StO2 and PbtO2 is high (correlation coefficient ¼ 0.934), and
Fig. 2 e Time courses of changes in (A) oxyhemoglobin (DHbO2), (B) deoxyhemoglobin (DHbR), and (C) total hemoglobin (DHbT) corresponding to different impact forces. * Indicated significance.
their relationship was showed in Figure 5. The root mean square deviation of the estimated PbtO2 change is about 1.061. The infarction volume corresponding to different impact strengths and the infarction volumes with changes in HbO2 and PbtO2 in a period of time after TBI (range, 90e120 min; Fig. 6Ae6C) demonstrated that the infarction volume
4
j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 5 ) 1 e7
Fig. 3 e Time courses of changes in partial pressure of oxygen in brain tissue (DPbtO2) corresponding to different impact forces. * Indicated significance.
increased with increasing impact strength and that changes in HbO2 and PbtO2 decreased with increasing impact strength. The correlation between infarction volume and changes in HbO2 (Fig. 7A) and between the infarction volume and changes in PbtO2 (Fig. 7B) demonstrated that both oxygen-related
Fig. 5 e Relationship between changes in PtO2 and StO2 after traumatic brain injury. (Color version of figure is available online.)
parameters significant correlated with the infarction volume. The correlation coefficient between infarction volume and changes in HbO2 was 0.96, whereas that between the infarction volume and changes in PbtO2 was 0.92.
4.
Fig. 4 e Correlations between changes in partial pressure of oxygen in brain tissue (DPbtO2) and (A) oxyhemoglobin (DHbO2) and (B) deoxyhemoglobin after traumatic brain injury (TBI). (Color version of figure is available online.)
Discussions
Wirelessly and noninvasively monitoring the concentration changes of HbO2, HbR, and HbT by using NIRS may be useful for evaluating the state of TBI in the clinical setting [13]. NIRS offers several advantages over existing radiological techniques: (1) the radiation is nonionising, and therefore, reasonable doses can be repeatedly used without harm to the patient; (2) soft tissues can be potentially differentiated because of their different absorption or scattering coefficients; and (3) specific absorption by natural chromophores (such as oxyhemoglobin) brings functional information [15e19]. This study investigated variations in the hemoglobin parameters and PbtO2. All the relative concentration changes of hemoglobin parameters and the changes in PbtO2 dropped immediately after the impact point. Because the post-FPI apnea caused cerebral hypoxia and the impact strength led to a distortion or displacement of the cerebral vasculature, cerebral blood flow decreased immediately resulting in cerebral hypoperfusion [14,20]. In addition, brain tissue injury due to the impact increased the oxygen requirement to meet the demand of metabolism [21,22], and this was manifested as increased changes in HbR (Fig. 2). Thus, cerebral hyperperfusion occurred after the hypoperfusion because of an effective autoregulation [23e25], as manifested in changes in HbT after TBI (Fig. 2). However, with increasing extent of injury, the reperfusion of HbO2 was affected greatly (Fig. 2A). This may be because the injured tissues consumed more oxygen for recovery and metabolism, and the original trauma damaged the ability of HbO2 reperfusion. The FPI experiment produced a larger extent of injury with increasing impact strength. It affected the oxygen requirement of the injured tissue, whereas oxygen diffusion barriers reduced cellular oxygen delivery after injury [26,27]. Thus,
j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 5 ) 1 e7
5
Fig. 7 e Correlations between the infarction volume and changes in (A) oxyhemoglobin (DHbO2) and (B) partial pressure of oxygen in brain tissue (DPbtO2) in a period of time after traumatic brain injury (TBI; range, 90e120 min). (Color version of figure is available online.) Fig. 6 e (A) The infarction volume corresponding to different impact forces and with changes in (B) oxyhemoglobin (DHbO2) and (C) partial pressure of oxygen in brain tissue (DPbtO2) in a period of time after traumatic brain injury (TBI; range, 90e120 min). *Indicated significance. PbtO2 decreased with increasing impact strength after TBI as PbtO2 was affected by cerebral autoregulation (Fig. 3) [24,28]. But because the reperfusion of HbO2 decreased with increasing impact strength, the recovery of PbtO2 became worse. Among this, the tendency in the impact strengths of 2.0 atm also recovered slowly, which might because the extent of injury was more severe than that in impact strengths of 1.6 atm. The impact strengths of 2.4 atm resulted in the very severe injury and led to outcomes that were almost unrecoverable. NIRS can also be used in identifying the formation of intracranial hematoma or cerebral edema [29], but there have been limited investigations in the field which carried the biggest expectations of its usefulnessdthe clinical care and prediction of outcomes of the injured brain patients. This
research intended to investigate the relationships between the relative HbO2 and HbR concentrations after brain injury and brain tissue oxygenation represented by PbtO2. Changes in PbtO2 positively and highly correlated to changes in HbO2. However, the correlation between changes in PbtO2 and changes in HbR was lower. This may be explained by the increased oxygen demand of the injured brain tissue as the injured brain needs more oxygen for repair. With higher oxygen demand of the injured brain tissue, more HbO2 is consumed. Simultaneously, the severity of injury also affects the level of changes in PbtO2. Otherwise, the correlation between changes in PbtO2 and changes in HbR is lower, which can be explained by the change in HbR being a coefficient related to oxygen consumption and cell metabolism. The higher change in HbR reflects a greater requirement of metabolism. Thus, the correlation between changes in PbtO2 and changes in HbR is low. Abernam [30] investigated the derivation formula between PbtO2 and StO2 and showed that the PbtO2 concentration is positively proportional to the StO2 concentration. Therefore, our experimental results fit the above mentioned results, and the change tendency of PbtO2 in
6
j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 5 ) 1 e7
TBI exactly can be estimated by the change of HbO2 and HbT measured by the proposed system noninvasively. In addition, according to increased impact strength, the demand and consumption of oxygen are heightened. With increased impact strength, changes in HbO2 and changes in PbtO2 are lower (Fig. 6B and C) because the introduced oxygen in autoregulation is consumed faster with the more severe extent of injury. To investigate this relationship more clearly, the relationships between infarction volume and the oxygenrelated parameters like changes in HbO2 and changes in PbtO2 (Fig. 7A and B). Changes in HbO2 and changes in PbtO2 are both negatively and highly related to the infarction volume, with the correlation coefficient between infarction volume and changes in HbO2 is 0.96 and that between infarction volume and changes in PbtO2 is 0.92. On the other hand, the extent of injury after 3 d may be related to the cerebral oxygenation in the acute phase, so cerebral oxygenation in the acute phase has to be treated carefully.
5.
Conclusions
In different severities of brain injury, changes in HbO2 are highly and positively correlated to changes in PbtO2. The proposed wireless NIRS system can be used to noninvasively estimate cerebral hypoxia. As such, the relative concentration changes of HbO2 may be used as the reference parameter to estimate the partial pressure of oxygen in the brain tissue.
Acknowledgment The authors thank the Chi Mei Medical Center and Institute of Photonic System, Imaging and Biomedical Photonics, and Lighting and Energy Photonics, National Chiao-Tung University, Tainan, Taiwan, for their instrumental support. The authors are also greatly indebted to the Ministry of Science and Technology, Taiwan, for the support of the research through contracts in 103-2221-E-009-035-MY2. Authors’ contributions: C.-C.W. contributed in article writing and data collection. J.-R.K., C.-C.C., and J.-J.W. provided experimental support. Y.-C.C. contributed to instrument preparation and data collection. B.-S.L. performed whole experiment design and article writing.
Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in the article.
references
[1] Jobsis FF. Non-invasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 1977;198:1264. [2] Lloyd-Fox S, Blasi A, Elwell CE. Illuminating the developing brain: the past, present and future of functional near infrared spectroscopy. Neurosci Biobehav Rev 2010;34:269.
[3] Pennekamp CW, Bots ML, Kappelle LJ, Moll FL, Borst GJ. The value of near-infrared spectroscopy measured cerebral oximetry during carotid endarterectomy in perioperative stroke prevention: a review. Eur J Vasc Endovasc Surg 2009; 38:539. [4] Joshi B, Ono M, Brown C, Brady K, Easley RB, Yenokyan G. Predicting the limits of cerebral autoregulation during cardiopulmonary bypass. Anesth Analg 2012;114:503. [5] Wolf T, Lindauer U, Reuter U, et al. Non-invasive near infrared spectroscopy monitoring of regional cerebral blood oxygenation changes during peri-infarct depolarizations in focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 1997;17:950. [6] Tsuji M, Duplessis A, Taylor G, Crocker R, Volpe JJ. Near infrared spectroscopy detects cerebral ischemia during hypotension in piglets. Pediatr Res 1998;44:591. [7] Kurth CD, Levy WJ, McCann J. Near-infrared spectroscopy cerebral oxygen saturation thresholds for hypoxia-ischemia in piglets. J Cereb Blood Flow Metab 2002;22:335. [8] Petrova A, Mehta R. Near-infrared spectroscopy in the detection of regional tissue oxygenation during hypoxic events in pre-term infants undergoing critical care. Pedia Crit Care Med 2006;7:449. [9] Merzagora AC, Schultheis MT, Onaral B, Izzetoglu M. Functional near-infrared spectroscopy-based assessment of attention impairments after traumatic brain injury. J Innovative Opt Health Sci 2011;4:251. [10] Quaresima V, Lepanto R, Ferrari M. The use of near infrared spectroscopy in sports medicine. J Sports Med Phys Fitness 2003;43:1. ska M, Silver IA. Tissue oxygen tension and brain [11] Erecin sensitivity to hypoxia. Respir Physiol 2001;128:263. [12] Dixon CE, Lyeth BG, Povlishock JT, et al. A fluid percussion model of experimental brain injury in the rat. J Neurosurg 1987;67:110. [13] Kuo JR, Lin BS, Cheng CL, Chio CC. Hypoxic-state estimation of brain cells by using wireless near-infrared spectroscopy. IEEE J Biomed Health Inform 2014;18:167. [14] Martin NA, Patwardhan RV, Alexander MJ, et al. Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm. J Neurosurg 1997;87:9. [15] Boas DA, Gaudette T, Strangman G, Cheng X, Marota JA, Mandeville JB. The accuracy of the near infrared spectroscopy and imaging during focal changes in cerebral hemodynamics. Neuroimage 2001;1:76. [16] Franceschini MA, Gratton E, Hueber D, Fantini S. Nearinfrared absorption and scattering spectra of tissues in vivo. Proc SPIE 1999;3597:52. [17] Herrmann MJ, Ehlis AC, Fallgatter AJ. Prefrontal activation through task requirements of emotional induction measured with NIRS. Biol Psychol 2003;64:255. [18] Tanosaki M, Sato C, Shimada M, Hoshi Y. Effect of stimulus frequency on human cerebral hemodynamic responses to electric median nerve stimulation: a NIRS study. Neurosci Lett 2003;352:1. [19] Francesco C, Andrea B, Maurizio D, Christian H, Luigi R. Noninvasive in vivo infrared laser spectroscopy to analyse endogenous oxy-haemoglobin, deoxy-haemoglobin, and blood volume in the rat CNS. J Neurosci Methods 2005;145:11. [20] Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth 2007;99:4. [21] Marchal G, Young AR, Baron JC. Early postischemic hyperperfusion: pathophysiologic insights from positron emission tomography. J Cereb Blood Flow Metab 1999;19: 467. [22] Vespa P, Bergsneider M, Hattori N, et al. Metabolic crisis without brain ischemia is common after traumatic brain
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injury: a combined micro-dialysis and positron emission tomography study. J Cereb Blood Flow Metab 2005;25:763. [23] Sakas DE, Bullock MR, Patterson J, Hadley D, Wyper DJ, Teasdale GM. Focal cerebral hyperemia after focal head injury in humans: a benign phenomenon? J Neurosurg 1995; 83:277. [24] Lang EW, Czosnyka M, Mehdorn HM. Tissue oxygen reactivity and cerebral auto-regulation after severe traumatic brain injury. Crit Care Med 2003;31:267. [25] Kelly DF, Kordestani RK, Martin NA, et al. Hyperemia following traumatic brain injury: relationship to intracranial hypertension and outcome. J Neurosurg 1996;85:762.
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[26] Nortje J, Gupta AK. The role of tissue oxygen monitoring in patients with acute brain injury. Br J Anaesth 2006;97:95. [27] Menon DK, Coles JP, Gupta AK, et al. Diffusion limited oxygen delivery following head injury. Crit Care Med 2004;32:1384. [28] Zweifel C, Dias C, Smielewski P, Czosnyka M. Continuous time-domain monitoring of cerebral auto-regulation in neuro-critical care. Med Eng Phys 2014;36:638. [29] Gill AS, Rajneesh KF, Owen CM, Yeh J, Hsu M, Binder DK. Early optical detection of cerebral edema in vivo. J Neurosurg 2011;114:470. [30] Aberman A. An equation for the oxygen hemoglobin dissociation curve. J Appl Phys 1973;35:570.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Brain tissue oxygen evaluation by wireless near-infrared spectroscopy Che-Chuan Wang, MD,a,b,c,d Jinn-Rung Kuo, MD, PhD,b,c,e Yu-Chih Chen, BS,f Chung-Ching Chio, MD,c Jhi-Joung Wang, MD, PhD,b and Bor-Shyh Lin, PhDb,f,* a
Institute of Photonic System, National Chiao-Tung University, Tainan, Taiwan Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan c Division of Neurosurgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan d Department of Child Care, Southern Taiwan University of Science and Technology, Tainan, Taiwan e Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan f Institute of Imaging and Biomedical Photonics, National Chiao-Tung University, Tainan, Taiwan b
article info
abstract
Article history:
Background: Monitoring the partial pressure of oxygen in brain tissue (PbtO2) is an impor-
Received 12 May 2015
tant tool for traumatic brain injury (TBI) but is invasive and inconvenient for real time
Received in revised form
monitoring. Near-infrared spectroscopy (NIRS), which can monitor hemoglobin parameters
14 September 2015
in the brain tissue, has been used widely as a noninvasive tool for assessing cerebral
Accepted 2 October 2015
ischemia and hypoxia. Therefore, it may have the potential as a noninvasive tool for
Available online xxx
estimating the change of PbtO2. In this study, a novel wireless NIRS system was designed to monitor hemoglobin parameters of rat brains under different impact strengths and was
Keywords:
used to estimate the change of PbtO2 noninvasively in TBI.
Traumatic brain injury
Materials and methods: The proposed wireless NIRS system and a PbtO2 monitoring system
Partial pressure of oxygen in brain
were used to monitor the oxygenation of rat brains under different impact strengths. Rats
tissue
were randomly assigned to four different impact strength groups (sham, 1.6 atm, 2.0 atm,
Near-infrared spectroscopy
and 2.4 atm; n ¼ 6 per group), and the relationships of concentration changes in oxyhe-
Oxyhemoglobin
moglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (HbT), and PbtO2 during
Deoxyhemoglobin
and after TBI with different impact strengths were investigated. Triphenyltetrazolium chloride (TTC) staining was also used to evaluate infarction volume. Results: Concentration changes in HbO2, HbR, and HbT dropped immediately after the impact, increased gradually, and then became stable. Changes in PbtO2 had a similar tendency with the hemoglobin parameters. There was significant correlation between changes in PbtO2 and HbO2 (correlation ¼ 0.76) but not with changes in HbR (correlation ¼ 0.06). In triphenyltetrazolium chloride staining, the infarction volume was highly but negatively associated with oxygen-related parameters like PbtO2 and HbO2. Conclusions: Changes in HbO2 under TBI was highly and positively correlated with changes in PbtO2. By using the relative changes in HbO2 as a reference parameter, the proposed
* Corresponding author. Institute of Imaging and Biomedical Photonics, National Chiao-Tung University, No.301, Gaofa 3rd Rd., Guiren Dist., Tainan City 711, Taiwan. Tel.: þ886 9 10181308; fax: þ886 6 2828928. E-mail address: [email protected] (B.-S. Lin). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2015.10.005
2
j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 5 ) 1 e7
wireless NIRS system may be developed as a noninvasive tool for estimating the change of PbtO2 in brain tissue after TBI. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
The partial pressure of oxygen in brain tissue (PbtO2) is usually used to evaluate the cerebral oxygenation of patients after traumatic brain injury (TBI), because the oxygenation of the injured tissue has a significant influence on recovery and outcome. Therefore, monitoring PbtO2 is an important tool for TBI patients clinically. However, PbtO2 monitoring is an invasive approach and may increase the risk of brain hemorrhage and infection. It is also inconvenient for real time monitoring. Recently, near-infrared spectroscopy (NIRS) was proposed by Jobsis in 1977 [1]. The method of near-infrared spectroscopy has been well established in neonatal care [2], carotid [3], and cardiac surgery [4]. NIRS has been used as a noninvasive real-time measurement of cerebral ischemia and hypoxia [5e8] and is also widely used in neuroscience for mapping the cerebral situation and assessing postinjury cognitive functions [9]. NIR light (700e1000 nm) penetrates skin, subcutaneous fat, and underlying muscle and is either absorbed (by oxyhemoglobin and deoxyhemoglobin) or scattered within the tissue [10]. Both the NIRS system and the PbtO2 monitoring system are used to assess physiological parameters related to the oxygen status of the brain. The measuring value of the PbtO2 monitoring system can directly reflect the status of tissue oxygen in the brain [11]. The parameters obtained by the NIRS system are related to the relative concentration of hemoglobin, such as oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (HbT), in brain tissue. Therefore, the relative concentrations of HbO2 and HbR can be related to the status of tissue oxygen. The hypothesis of this study is that the change of NIRS parameters may be highly correlated to the change of PbtO2. In this study, a wireless NIRS system was designed and implemented to monitor the changes of relative concentrations of HbO2, HbR, and HbT during and after TBI. The relationships of the concentration changes of HbO2 and HbR, and PbtO2 during and after TBI were also investigated. The relationship between hemoglobin parameters and PbtO2 under different impact strengths proves that the technique of NIRS has the potential as a noninvasive tool for estimating the change of PbtO2.
2.
Materials and methods
2.1.
Animal preparation
Twenty-four adult male SpragueeDawley rats weighing 325e375 g were fostered under a 12-h light and/or dark cycle and allowed to ad libitum access to water and food. All the experimental procedures conformed to the guidelines of the National Institute of Health, Taiwan, and were approved by the Animal Care and Use Committee of Chi-Mei Medical Center.
All the rats were randomly divided to four different impact groups (sham, 1.6 atm, 2.0 atm, and 2.4 atm) in the fluid percussion injury experiments and monitored by the NIRS system and the PbtO2 monitoring system (OxyLite 2000, Oxford Optronix). The rats were anesthetized with a sodium pentothal (25 mg/kg, i.p.; Sigma Chemical Co, St. Louis, MO) and a mixture containing ketamine (44 mg/kg, i.m.; Nan Kuang Pharmaceutical, Tainan, Taiwan), atropine (0.02633 mg/kg, i.m.; Sintong Chemical Industrial Co, Ltd, Taoyuan, Taiwan), and xylazine (6.77 mg/kg, i.m.; Bayer, Leverkusen, Germany) before the experiment. The rats were sacrificed on the third day after surgery.
2.2.
Experiment design for traumatic brain injury
The fluid percussion injury (FPI) experimental model was used as the TBI model of the rats [12]. Before the experiment, the rat was anesthetized, and the head was tied with ear bars inserted in a stereotaxic frame. To hold the rat core temperature at 37 C, a rectal temperature probe was set into the rat’s colon, and the rat was placed on a heating pad that was controlled by the thermostatic controller. The fur on the rat head was then shaved and its scalp incised sagittally. A circular hole was located and drilled on the skull to situate the impact point at 3 mm anterior-posterior and þ4 mm lateral to the bregma. A luer-lock connector was connected to a sealed and fluid-filled reservoir and fixed into the craniotomy with cyano-acrylic adhesive and dental acrylic. The monitoring systems (wireless NIRS system [13] and OxyLite 2000) were set up, including the positions of the optical measuring probe of the wireless NIRS system, the PbtO2 barefiber sensor, and the luer-lock connector. The PbtO2 bare-fiber sensor was placed nearby the luer lock and was inserted to the striatum region under stereotactic frame. The photodiode and light-emitting diode were set up at 8 mm away from the drill hole of the PbtO2 sensor (Fig. 1). Before the experiment, the relative concentrations of HbO2, HbR, and PbtO2 were monitored continuously for 30 min until the rat became stable.
Fig. 1 e Illustration for locations of luer-lock connector, near-infrared spectroscopy optical measuring probe, and partial pressure of oxygen in brain tissue bare-fiber sensor on rat skull. (Color version of figure is available online.)
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Baseline data were set by the 5-min raw data before the FPI experiment. A fluid wave was then generated to impact the rat brain like a pendulum that struck the reservoir. After FPI, the tongue of rats would be pulled out immediately to help the rat breathing (respiratory treatment). During the whole experimental procedure, these monitoring systems recorded continuously for 2 h. At the end of the experiment, the connector and acrylic were removed from the rat head, and the incisions on the rat were sutured.
2.3.
Cerebral infarction assay
In this study, the brain injury area was analyzed by triphenyltetrazolium chloride staining [14]. All the rats were sacrificed at 72 h after TBI. The brains of the TBI rats were taken for staining, and the infarction volume was measured by using the computerized planimetry (PC-based Image Tools software). The infarction volume was expressed as [the thickness of each slice (2 mm)] [the sum of the infarction region in all of the slices (mm2)].
2.4.
Statistical analysis
The time courses data of HbO2, HbR, and PbtO2 and the infarction volume in different groups were analyzed by analysis of variance. Statistical significance was set at P < 0.05. The linear correlation coefficients between PbtO2 and HbO2 and between PbtO2 and HbR were analyzed using MATLAB (MathWorks, Natick, MA).
3.
Results
With different impact strengths, the time courses of the relative concentration changes of HbO2, HbR, and HbT revealed that these all dropped immediately after the impact point (Fig. 2Ae2C). After applying a respiratory treatment, the relative concentration changes of HbO2, HbR, and HbT increased gradually and then became stable. The lower impact strength caused a higher increasing tendency of these parameters. Moreover, all these changes rose higher after TBI compared to their baseline values, except for the change in HbO2 under the impact strength of 2.4 atm. The time courses of changes in PbtO2 corresponding to different impact strengths demonstrated that the change of PbtO2 dropped immediately at the impact point in all the impact strengths (Fig. 3). This change tendency was similar to the tendencies of the NIRS parameters. In the 1.6 atm group, the change in PbtO2 reverted to near baseline level within 10 min (after respiratory treatment). In the 2.0 atm group, the change in PbtO2 was back near the baseline level later, but in the group of 2.4 atm, the change in PbtO2 remained in the lower levels even after 2 h. In addition, the result of correlation between changes in PbtO2 and in HbO2 (Fig. 4A) and the correlation between changes in PbtO2 and in HbR (Fig. 4B) revealed that the change in PbtO2 significant correlated with the change in HbO2 (correlation coefficient ¼ 0.76) but not with the change in HbR (correlation coefficient ¼ 0.06). The correlation between the change of StO2 and PbtO2 is high (correlation coefficient ¼ 0.934), and
Fig. 2 e Time courses of changes in (A) oxyhemoglobin (DHbO2), (B) deoxyhemoglobin (DHbR), and (C) total hemoglobin (DHbT) corresponding to different impact forces. * Indicated significance.
their relationship was showed in Figure 5. The root mean square deviation of the estimated PbtO2 change is about 1.061. The infarction volume corresponding to different impact strengths and the infarction volumes with changes in HbO2 and PbtO2 in a period of time after TBI (range, 90e120 min; Fig. 6Ae6C) demonstrated that the infarction volume
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Fig. 3 e Time courses of changes in partial pressure of oxygen in brain tissue (DPbtO2) corresponding to different impact forces. * Indicated significance.
increased with increasing impact strength and that changes in HbO2 and PbtO2 decreased with increasing impact strength. The correlation between infarction volume and changes in HbO2 (Fig. 7A) and between the infarction volume and changes in PbtO2 (Fig. 7B) demonstrated that both oxygen-related
Fig. 5 e Relationship between changes in PtO2 and StO2 after traumatic brain injury. (Color version of figure is available online.)
parameters significant correlated with the infarction volume. The correlation coefficient between infarction volume and changes in HbO2 was 0.96, whereas that between the infarction volume and changes in PbtO2 was 0.92.
4.
Fig. 4 e Correlations between changes in partial pressure of oxygen in brain tissue (DPbtO2) and (A) oxyhemoglobin (DHbO2) and (B) deoxyhemoglobin after traumatic brain injury (TBI). (Color version of figure is available online.)
Discussions
Wirelessly and noninvasively monitoring the concentration changes of HbO2, HbR, and HbT by using NIRS may be useful for evaluating the state of TBI in the clinical setting [13]. NIRS offers several advantages over existing radiological techniques: (1) the radiation is nonionising, and therefore, reasonable doses can be repeatedly used without harm to the patient; (2) soft tissues can be potentially differentiated because of their different absorption or scattering coefficients; and (3) specific absorption by natural chromophores (such as oxyhemoglobin) brings functional information [15e19]. This study investigated variations in the hemoglobin parameters and PbtO2. All the relative concentration changes of hemoglobin parameters and the changes in PbtO2 dropped immediately after the impact point. Because the post-FPI apnea caused cerebral hypoxia and the impact strength led to a distortion or displacement of the cerebral vasculature, cerebral blood flow decreased immediately resulting in cerebral hypoperfusion [14,20]. In addition, brain tissue injury due to the impact increased the oxygen requirement to meet the demand of metabolism [21,22], and this was manifested as increased changes in HbR (Fig. 2). Thus, cerebral hyperperfusion occurred after the hypoperfusion because of an effective autoregulation [23e25], as manifested in changes in HbT after TBI (Fig. 2). However, with increasing extent of injury, the reperfusion of HbO2 was affected greatly (Fig. 2A). This may be because the injured tissues consumed more oxygen for recovery and metabolism, and the original trauma damaged the ability of HbO2 reperfusion. The FPI experiment produced a larger extent of injury with increasing impact strength. It affected the oxygen requirement of the injured tissue, whereas oxygen diffusion barriers reduced cellular oxygen delivery after injury [26,27]. Thus,
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Fig. 7 e Correlations between the infarction volume and changes in (A) oxyhemoglobin (DHbO2) and (B) partial pressure of oxygen in brain tissue (DPbtO2) in a period of time after traumatic brain injury (TBI; range, 90e120 min). (Color version of figure is available online.) Fig. 6 e (A) The infarction volume corresponding to different impact forces and with changes in (B) oxyhemoglobin (DHbO2) and (C) partial pressure of oxygen in brain tissue (DPbtO2) in a period of time after traumatic brain injury (TBI; range, 90e120 min). *Indicated significance. PbtO2 decreased with increasing impact strength after TBI as PbtO2 was affected by cerebral autoregulation (Fig. 3) [24,28]. But because the reperfusion of HbO2 decreased with increasing impact strength, the recovery of PbtO2 became worse. Among this, the tendency in the impact strengths of 2.0 atm also recovered slowly, which might because the extent of injury was more severe than that in impact strengths of 1.6 atm. The impact strengths of 2.4 atm resulted in the very severe injury and led to outcomes that were almost unrecoverable. NIRS can also be used in identifying the formation of intracranial hematoma or cerebral edema [29], but there have been limited investigations in the field which carried the biggest expectations of its usefulnessdthe clinical care and prediction of outcomes of the injured brain patients. This
research intended to investigate the relationships between the relative HbO2 and HbR concentrations after brain injury and brain tissue oxygenation represented by PbtO2. Changes in PbtO2 positively and highly correlated to changes in HbO2. However, the correlation between changes in PbtO2 and changes in HbR was lower. This may be explained by the increased oxygen demand of the injured brain tissue as the injured brain needs more oxygen for repair. With higher oxygen demand of the injured brain tissue, more HbO2 is consumed. Simultaneously, the severity of injury also affects the level of changes in PbtO2. Otherwise, the correlation between changes in PbtO2 and changes in HbR is lower, which can be explained by the change in HbR being a coefficient related to oxygen consumption and cell metabolism. The higher change in HbR reflects a greater requirement of metabolism. Thus, the correlation between changes in PbtO2 and changes in HbR is low. Abernam [30] investigated the derivation formula between PbtO2 and StO2 and showed that the PbtO2 concentration is positively proportional to the StO2 concentration. Therefore, our experimental results fit the above mentioned results, and the change tendency of PbtO2 in
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TBI exactly can be estimated by the change of HbO2 and HbT measured by the proposed system noninvasively. In addition, according to increased impact strength, the demand and consumption of oxygen are heightened. With increased impact strength, changes in HbO2 and changes in PbtO2 are lower (Fig. 6B and C) because the introduced oxygen in autoregulation is consumed faster with the more severe extent of injury. To investigate this relationship more clearly, the relationships between infarction volume and the oxygenrelated parameters like changes in HbO2 and changes in PbtO2 (Fig. 7A and B). Changes in HbO2 and changes in PbtO2 are both negatively and highly related to the infarction volume, with the correlation coefficient between infarction volume and changes in HbO2 is 0.96 and that between infarction volume and changes in PbtO2 is 0.92. On the other hand, the extent of injury after 3 d may be related to the cerebral oxygenation in the acute phase, so cerebral oxygenation in the acute phase has to be treated carefully.
5.
Conclusions
In different severities of brain injury, changes in HbO2 are highly and positively correlated to changes in PbtO2. The proposed wireless NIRS system can be used to noninvasively estimate cerebral hypoxia. As such, the relative concentration changes of HbO2 may be used as the reference parameter to estimate the partial pressure of oxygen in the brain tissue.
Acknowledgment The authors thank the Chi Mei Medical Center and Institute of Photonic System, Imaging and Biomedical Photonics, and Lighting and Energy Photonics, National Chiao-Tung University, Tainan, Taiwan, for their instrumental support. The authors are also greatly indebted to the Ministry of Science and Technology, Taiwan, for the support of the research through contracts in 103-2221-E-009-035-MY2. Authors’ contributions: C.-C.W. contributed in article writing and data collection. J.-R.K., C.-C.C., and J.-J.W. provided experimental support. Y.-C.C. contributed to instrument preparation and data collection. B.-S.L. performed whole experiment design and article writing.
Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in the article.
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