|Year : 2019 | Volume
| Issue : 1 | Page : 12-19
Multimodal Monitoring Technologies for Pathophysiology and Management of Traumatic Brain Injury
Yujie Chen1, Qianwei Chen1, Jian Sun2, Lijun Zhang3, Liang Tan1, Hua Feng1
1 Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China
2 Department of Neurosurgery, Southwest Hospital, Third Military Medical University; College of Biomedical Engineering, Third Military Medical University, Chongqing, China
3 Department of Neurosurgery, Chongqing Municipal Emergency Medical Center, Chongqing, China
|Date of Web Publication||4-Jan-2019|
Dr. Hua Feng
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038
Despite decades of efforts, severe traumatic brain injury (TBI) is still the leading cause for mortality and immobility of children and young adults worldwide and is a great burden to the health-care system. After injury, the oxygen supply is conventionally considered the monitoring parameter in a neurosurgical Intensive Care Unit. However, the overall mortality rate has only slightly improved since the late twentieth century. Evolving evidence suggests that dysfunction of oxygen utilization might be the underlying pathophysiology of secondary brain injury, which should also be a key parameter for multimodal monitoring and management after severe TBI. In this review, we summarize the current and advanced understanding of multimodal monitoring for severe TBI along with novel noninvasive technologies in this field. By continuously monitoring patients with severe TBI, the use of multimodal monitoring technologies including (but not limited to) computed tomography, cerebral microdialysis, near-infrared spectroscopy, magnetic resonance spectroscopy, high-performance liquid chromatography, and magnetic induction phase shift method will be crucial for observing disease changes such as intracranial pressure and brain tissue oxygen partial pressure as well as developing potential therapeutic strategies after severe TBI.
Keywords: Mitochondrial dysfunction, multimodal monitoring, oxygen utilization, secondary brain injury, traumatic brain injury
|How to cite this article:|
Chen Y, Chen Q, Sun J, Zhang L, Tan L, Feng H. Multimodal Monitoring Technologies for Pathophysiology and Management of Traumatic Brain Injury. J Transl Crit Care Med 2019;1:12-9
|How to cite this URL:|
Chen Y, Chen Q, Sun J, Zhang L, Tan L, Feng H. Multimodal Monitoring Technologies for Pathophysiology and Management of Traumatic Brain Injury. J Transl Crit Care Med [serial online] 2019 [cited 2021 May 14];1:12-9. Available from: http://www.tccmjournal.com/text.asp?2019/1/1/12/249335
| Introduction|| |
Despite decades of efforts, severe traumatic brain injury (TBI) is still the leading cause for mortality and disability of children and young adults worldwide and is a great burden to the health-care system. Key pathophysiological processes of TBI are initiated by mechanical forces at the onset of trauma, followed by complex detrimental cascades associated with secondary insults. However, the overall mortality rate of individuals suffering from TBI has only slightly improved since the late twentieth century. Evolving evidence has suggested that dysfunction of oxygen utilization might be the underlying pathophysiology of secondary brain injury, which should be the focal point for multimodal monitoring and management after severe TBI., In this review, we summarize the current understanding of multimodal monitoring for severe TBI along with the novel noninvasive technologies available in this field. By continuously monitoring the patients with severe TBI, multimodal monitoring technologies could provide neurointensivists and neurosurgeons valuable information about the changes and thresholds of physiological parameters that act as surrogates of brain ischemia, hypoxia, and mitochondrial dysfunction, all of which are the major causes for secondary brain injury after TBI.
| Secondary Brain Injury after Traumatic Brain Injury for Neuromonitoring|| |
Similar to other acute central nervous system injuries, TBI can be divided into two major pathophysiological phases: primary injury and secondary injury. The primary injury is the initial neuronal injury that occurs immediately and is a direct result of the traumatic insults, which are classified as mild (13–15 points), moderate (8–12 points), or severe (3–8 points) by the Glasgow Coma Scale. At the macroscopic level, damage includes shearing of white matter tracts, focal contusions, hematomas, and diffuse edema.,, At the cellular level, early consequences of neurotrauma include leaky ion channels, conformational changes of proteins, and microhemorrhages.,, If the primary injury is untreatable, it often proves fatal.
The secondary injury develops over hours to days after the initial trauma and includes excitotoxicity, free radical generation, damage due to calcium overload, blood–brain barrier disruption, disrupted pathway cascades, ischemia, mitochondrial dysfunction, and neuroinflammation.,, These pathophysiologies of TBI are multifaceted and heterogeneous and must be considered when designing neuroprotective treatments; furthermore, the broad pathologies might partially explain why neuroprotective therapies have not shown significant clinical benefit in humans to date. Among these interlaced mechanisms, ischemia and hypoxia play critical roles in the secondary brain injury after TBI. Therefore, the focus of monitoring in an Intensive Care Unit (ICU) should be parameters that can act as surrogates of brain ischemia and hypoxia. Increasing evidence indicates that reduced brain tissue oxygen pressure (PbtO2) indicates a worse prognosis for patients with TBI.,, Furthermore, increased intracerebral pressure (ICP) caused by blood–brain barrier disruption and cell swelling is still considered the fundamental parameter of monitoring after TBI and is indicative of brain edema and ischemia with regard to the progression of secondary brain injury via inadequate cerebral perfusion and oxygenation.,,
| The Current Understandings and Limitations of Multimodal Monitoring|| |
After injury, the oxygen supply is conventionally considered as the core parameter for monitoring in a neurosurgical ICU. Continuous monitoring of brain oxygen tension revealed that approximately one-third of patients severe TBI who had reduced brain oxygen tension (<25 mmHg O2) for the first 6–12 h had significantly worse outcomes., Real-time dynamic monitoring of cerebral oxygenation is essential for an early diagnosis to reverse brain ischemia and hypoxia.
Due to its fundamental role in the care of patients with severe TBI and its relationship with overall outcomes, ICP monitoring has been included in every guideline for severe TBI published by the Brain Trauma Foundation. The clinical value of ICP monitoring includes (1) earlier detection of intracranial mass lesions, (2) therapy guidance and avoidance of the indiscriminate use of therapies to control ICP, (3) drainage of cerebrospinal fluid to reduce the ICP and improve the cerebral perfusion pressure (CPP), and (4) determination of the prognosis of TBI patients., In developed countries, ICP monitoring is routinely used, leading to “a lack of clinical equipoise for assigning patients to a nonmonitored arm of potential interventional trials.” Therefore, tremendous evidence supporting the utility of ICP monitoring is observational and largely suggests that ICP crises led to poorer outcomes. However, there is still controversy regarding ICP monitoring after TBI. The well-known BEST: TRIP trial indicated that ICP monitoring could not significantly improve early- or long-term survival by comparing to computed tomography (CT) and clinical observation. However, there were several limitations in this trial such as a shortage of prehospital emergency treatments in South America and differences in the ICU facilities and equipment. In addition, irregular ICP monitoring was employed in this trial, and only 37% of studied patients had an initial ICP value >20 mmHg. Furthermore, the monitoring position was the brain parenchyma instead of the lateral cerebral ventricles with average monitoring time of only 3.6 days (2.0–6.6 days). Other researchers suggest that, based on the ICP, posttraumatic monitoring could effectively improve prognosis but was accompanied by increased incidence of meningitis incidence. So far, the methods of ICP monitoring include implants in the epidural space, subarachnoid space, or brain parenchyma or an intraventricular catheter as well as several noninvasive methods such as bregmatic fontanel manometry, transcranial Doppler sonography, measurement of retinal venous pressure, flash-visual evoked potential, and electrical bioimpedance. However, only implanted ICP monitors were relatively accurate in detecting changes of the intracranial pressure with an increased infection risk due to probe implantation.
PbtO2 is another reliable technique for monitoring focal cerebral oxygenation to prevent episodes of desaturation. To monitor this parameter, a tiny electrode is introduced into the brain parenchyma and samples a very small area (i.e., a cubic millimeter). During selected time periods with more dynamic changes in PbtO2, a positive correlation between the CPP and PbtO2 is more apparent., This may indicate that an increasing CPP could possibly improve brain tissue oxygenation. A systematic review of the efficacy of PbtO2-based therapy for severe TBI shows that combined ICP/CPP-based and PbtO2-based therapies are associated with better outcomes than those of ICP/CPP-based therapy alone., However, the main problem with PbtO2 is that it changes dramatically in different regions of the brain. Valadka et al. illustrated a tight correlation between PbtO2 and jugular bulb blood oxygenation only in areas without focal injury; however, in areas with focal injury, this correlation is absent. Furthermore, near-infrared spectroscopy might become a new tool for the continuous, direct, and noninvasive monitoring for detecting cerebral oxygenation after severe TBI.,,
Despite in-depth ICP monitoring and satisfactory ICP/CPP management, 30% of the mortality cannot be explained with brain tissue hypoxia alone., Why do TBI patients with normal CPP and PbtO2 still have a poor prognosis? Evolving evidence suggests that dysfunction of oxygen utilization might be the underlying pathophysiology of secondary brain injury, and the mitochondrial dysfunction is the pivotal aspect for multimodal monitoring and management after severe TBI. Since mitochondria are ubiquitous in all cells, disrupting cellular metabolism is implicated in almost all areas of critical illness. This is especially in neurocritical care since mitochondrial dysfunction occurs both in acute and chronic neurodegenerative disorders., In particular, energetic failure is one of the most important mechanisms responsible for brain damage early after a TBI. Evidence for mitochondrial dysfunction after severe TBI is profound and includes altered mitochondrial morphology, depressed mitochondrial activities, loss of the mitochondrial electron transport system, dissipation of the membrane potential, release of mitochondrial proapoptotic proteins, and N-acetylaspartate reduction based on magnetic resonance spectroscopy. Structural damage is expressed in terms of swollen mitochondria, fragmented cristae, expanded matrix compartment, and rupture of outer membrane, which are indicative of the onset of the loss of ΔΨm.
Mitochondrial dysfunction in TBI patients is an active area of research, and attempts to manipulate neuronal and/or astrocytic metabolism to improve outcomes have been met with limited translational success. Uncoupling the tricarboxylic acid cycle results in pyruvate shifting toward aerobic glycolysis, and the resulting lactate accumulation after TBI might explain the poor outcomes under normal oxygen supply [Figure 1]. According to a microdialysis monitoring study in TBI patients, changes in glucose, lactate, pyruvate, lactate/pyruvate ratio, glycerol, and glutamate after TBI are associated with the patients' prognosis. Among these biochemical biomarkers in the extracellular fluid, glutamate and lactate/pyruvate ratio exhibited the best predictive value. Previously, several preclinical and clinical studies on preventing or reversing mitochondrial dysfunction and cellular metabolic failure after acute brain injury may represent a viable neuroprotective approach with either cyclosporine-A or other analogous drugs.,, Our animal studies also demonstrate that cyclosporine-A prevented the opening of the mitochondrial permeability transition pore and stabilized the mitochondrial outer membrane; this activity alleviated mitochondrial swelling and maintained mitochondrial structural integrity and native energy metabolism. Recent insight into mitochondrial dynamics and related diseases such as inherited mitochondrial neuropathies, sepsis, and organ failure could provide novel opportunities to develop mitochondria-based neuroprotective treatments that could improve severe TBI outcomes. However, these medications require large-scale, multicenter, prospective clinical trials to evaluate and verify their efficacy and safety in patients with TBI. Consequently, the central question in the care of critically ill patients “Do ICU patients die from mitochondrial failure?” should also be considered in the acute care of TBI patients.
|Figure 1: Differentiation between brain ischemia and mitochondrial dysfunction|
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| Hypothermia as a Controversial Management during Multimodal Monitoring|| |
Based on the data from several basic and clinical studies, therapeutic hypothermia has been conventionally considered as the candidate of neuroprotective treatment in neurological ICU, which was recommended in emergency medicine to protect against neurological injury following cardiac arrest due to the ventricular fibrillation., More recently, Liu et al. also demonstrate that therapeutic hypothermia could protect the injured central nervous system from tissue damage and the inflammatory responses by targeting the RIP1/RIP3-MLKL-mediated necroptosis after experimental TBI.
In addition to the neuroprotective effects, hypothermia is well known for its promising efficacy to reduce ICP after TBI. Previously, many single-center trials and meta-analyses support the therapeutic hypothermia (32°C–35°C) in attenuating secondary intracranial hypertension after TBI.,,, However, in 2015, a well-designed multicenter, randomized, controlled clinical trials did not show favorable outcomes with the use of therapeutic hypothermia in adult patients with TBI as compared to normothermia treatment, which raises many controversial opinions about the negative effect of hypothermia due to the randomization time or analysis power because of small samples in some teams.,,,,, In July 2016, a meta-analysis performed by Zhu et al. also shows that therapeutic hypothermia failed to provide a decrease in mortality and unfavorable clinical outcomes at 3 or 6 months after TBI. In addition, therapeutic hypothermia might increase the risk of developing pneumonia and cardiovascular complications. Therefore, the updated guidelines still not recommend therapeutic hypothermia for the patients with severe TBI.
Currently, in the clinical treatment, advanced temperature control devices are usually being added depending on the degree and severity of the febrile response after TBI. Several types of temperature control devices are available, including invasive (intravascular catheters) and noninvasive (external cooling pads) technologies, as well as the pharmacologic-based temperature therapies to minimize the time of febrile state, and help to alleviate the secondary brain injury due to the fever. Based on our previous study, the pharmacologic hypothermia might be a better solution for the management of TBI patients. We employed the 8-OH-DPAT (5-HT1α agonist) for 48 h in the rats of experiment intracerebral hemorrhage, which provides a similar but steadier reduction in the brain temperature without a withdrawal rebound [Figure 2], and exhibit superior neuroprotection on the blood–brain barrier permeability and perihematomal nerve fiber injury compared to the physical hypothermia group. Our data are supported by the pharmacological hypothermia study using neurotensin receptor agonist HPI201, which shows effective in alleviating neuronal and blood–brain barrier damage, suppression inflammatory response, and detrimental cellular signaling and promoting functional recovery after TBI.
|Figure 2: Intracerebral temperature changes after experimental ICH. Intracerebral temperature measured by surface near-infrared spectrum imaging at 6, 12, 24, and 72 h after ICH modeling in rats. Pharmacologic hypothermia induced by 8-OH-DPAT (5-HT1α agonist) provides a similar but steadier reduction in the brain temperature without a withdrawal rebound, by comparing to physical hypothermia. DPAT: 8-hydroxy-(2-dinpropylamino) tetralin hydrobromide, 8-OH-DPAT; HYPO: Physical hypothermia treatment; ICH: Intracerebral hemorrhage|
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Conclusively, therapeutic hypothermia is still at the center of neuroprotective treatments in TBI under the monitoring in neurologic ICU, which is expected to alleviate ischemic injury and reduce intracranial pressure for TBI. However, further high-power clinical trials are waited to provide more evidence to support its potential therapeutic effects for TBI patients.
| Potential Technology Developments in Multimodal Monitoring|| |
Magnetic induction phase shift method
The magnetic induction phase shift (MIPS), which is based on detecting characteristic parameters such as the conductivity of diseased tissue, is a noncontact, noninvasive, inexpensive, and portable method that can provide continuous bedside monitoring and is a recent development for detecting cerebral hemorrhage.,,,, The relevance of using MIPS here is the electromagnetic properties of biological tissues. As shown by Tarjan and McFee, electrode-free measurement of changing impedances in the human body could be achieved by measuring the effect of induced eddy currents. It has been established in the literature that different biological tissues have different electromagnetic properties and can therefore be distinguished on the basis of these properties. There are two types of techniques in MIPS research – the time difference method and the frequency difference method. The time difference method is used to detect phase shift differences before and after a simulated lesion occurs and can be used for monitoring purposes.,, The frequency difference method is self-referencing and can be performed over a short time to provide instantaneous information of a cerebral hemorrhage. Previous reports have described simulation studies of a magnetic induction tomography (MIT) measurement system, designed a new type of excitation source, implemented an optimal excitation coil for MIT, adopted the MIPS method for detecting normal and edema nerve cells, and conducted experimental studies on simulated cerebral edema detection by using MIPS. A system block diagram of the experimental setup using MIPS to detect changes is shown in [Figure 3].,
|Figure 3: Diagram of the experimental setup to detect the magnetic induction phase shift in conjunction with the intracranial pressure. (a) System block diagram of the MIPS detection method. The data include the HR and ICP. The ICP, HR, and MIPS were synchronously collected to compare the measured results. (b) Theoretic relationship between conductivity and ICP (P = P0eKAτθ) based on the brain model. The curves representing changes of the MIPS are mainly significantly related to changes in the ICP. This observation suggests that this method could be valuable as an early warning in emergency medicine and critical care units in addition to its role in continuous monitoring. MIPS: Magnetic induction phase shift; ICP: Intracerebral pressure; HR: Heart rate|
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Terahertz (THz) radiation generally refers to the frequency band spanning 0.1–10 THz, which lies between the microwave and infrared regions of the electromagnetic spectrum. The rapid development of ultrafast lasers contributed to the establishment of modern THz time-domain spectroscopy, which has been widely applied in astronomy, microelectronics, and biomedical science. THz = 1012 Hz radiation has attracted wide attention for its unprecedented sensing ability and its noninvasive and nonionizing properties. Tremendous strides in THz instrumentation have prompted impressive breakthroughs in THz biomedical research. THz imaging could be used as a tool for label-free and real-time imaging of brain tumors, which would be helpful for surgeons to determine tumor margins during brain surgery.,,
Polar molecules such as water exhibit strong absorption in the THz range. Specifically, the THz absorption coefficient of water at 1 THz is approximately 220 cm−1 at room temperature, exceeding that of other common biomolecules., Normal tissues and cancer tissues can be accurately differentiated because their water content is different. Moreover, THz radiation has the potential to rapidly assess the living state of bacteria (i.e., live or dead) according to their hydration levels. THz radiation incorporates characteristic frequency features with the spatial resolution of several micrometers by near-field spectroscopic modalities and reveals time-resolved dynamics on the sub-picosecond to picosecond timescales. Thus, THz spectroscopy permits time-resolved investigations of the collective vibration modes of biomolecules in solution with unprecedented sensing capability.,
The low-energy photons of THz radiation (i.e., ≈1–10 meV) make it suitable for medical imaging, because unlike X-rays, its noninvasive imaging modality can be applied to in vivo real-time diagnosis without causing ionization damage. Moreover, THz wavelengths are longer than infrared and visible light, and scattering losses in biological tissues are negligible. Because of these characteristics of THz spectroscopy, this modality has the potential for future noninvasive neuromonitoring for patients in a neurosurgical ICU.
Neurocritical care bioinformatics is a new field that focuses on the acquisition, storage, and analysis of physiological and other data relevant to the bedside care of patients with TBI. However, the ability to analyze these advanced data for real-time clinical care remains intuitive and primitive. Advanced statistical and mathematical tools are now being applied to the large volume of clinical and physiological data routinely monitored in neurocritical care with the goal of identifying better markers of brain injury and providing clinicians with an improved ability to target specific parameters in the management of these patients.
Advances in neuromonitoring technologies have been profound and now include the ability to directly monitor brain oxygenation, cerebral blood flow, and cerebral metabolism essentially in real time. Despite these advances, data from neurocritical care patients are evaluated by clinicians in much the same way as 40 years ago. Bioinformatics has fundamentally changed many fields in medicine, including epidemiology, genetics, and pharmacology.,,,, It acts as a platform to integrate other biomedical technologies to achieve multi-modal monitoring for patients with TBI. New tools for data acquisition, storage, and analysis are currently being applied to neurocritical care data to harness the large volume of data now available to clinicians. In this emerging field, neurocritical care bioinformatics require collaborations between clinicians, computer scientists, engineers, and informatics experts to bring user-friendly, real-time advances to the patient's bedside.
| Perspective and Conclusion|| |
Although technology over the past several decades has provided us with improved neuroimaging and advanced noninvasive and invasive neuromonitoring, the role of the bedside neurological examination is still the cornerstone of neuromonitoring. When neurological monitoring through clinical examination is possible, data obtained from multimodal monitoring should be interpreted in the context of the neurological examination. The traditional monitoring of the ICP does not fully reflect the dynamic process of secondary injury after TBI and sometimes does not provide accurate information for judgment, which limits the treatment options for the patient. By employing multimodal monitoring technologies [Figure 4] including but not limited to CT, ICP, PbtO2, cerebral microdialysis, near-infrared spectroscopy, magnetic resonance spectroscopy, high-performance liquid chromatography, and MIPS method, comprehensive monitoring of the biochemical conditions of the brain tissue might provide more valuable real-time information to analyze and better treat TBI patients. Nevertheless, these new technologies should be verified for its sensibility and specificity by multicenter clinical trials, as well as the correlations between its monitoring value and classical neuroimaging or invasive ICP values. With the progress of multi-modal monitoring technologies, we hope the big data of medical history, neuroimages, cerebral blood flow, brain metabolism, and brain function could be integrately provided and interpreted for the clinical management and therapeutic decision-making.
|Figure 4: Clinical value of multimodal monitoring for severe traumatic brain injury patients|
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Financial support and sponsorship
This work was supported by the National Basic Research Program of China (973 Program, Grant No. 2014CB541600) and the National Natural Science Foundation of China (Grant Nos. 81501002, 81220108009, and 51607181).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hemphill JC, Andrews P, De Georgia M. Multimodal monitoring and neurocritical care bioinformatics. Nat Rev Neurol 2011;7:451-60.
Stein SC, Georgoff P, Meghan S, Mizra K, Sonnad SS. 150 years of treating severe traumatic brain injury: A systematic review of progress in mortality. J Neurotrauma 2010;27:1343-53.
Carré JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M, et al.
Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med 2010;182:745-51.
Gajavelli S, Sinha VK, Mazzeo AT, Spurlock MS, Lee SW, Ahmed AI, et al.
Evidence to support mitochondrial neuroprotection, in severe traumatic brain injury. J Bioenerg Biomembr 2015;47:133-48.
Koskinen LO, Olivecrona M, Grände PO. Severe traumatic brain injury management and clinical outcome using the lund concept. Neuroscience 2014;283:245-55.
Sheriff FG, Hinson HE. Pathophysiology and clinical management of moderate and severe traumatic brain injury in the ICU. Semin Neurol 2015;35:42-9.
Chodobski A, Zink BJ, Szmydynger-Chodobska J. Blood-brain barrier pathophysiology in traumatic brain injury. Transl Stroke Res 2011;2:492-516.
McGinn MJ, Povlishock JT. Pathophysiology of traumatic brain injury. Neurosurg Clin N Am 2016;27:397-407.
Pearn ML, Niesman IR, Egawa J, Sawada A, Almenar-Queralt A, Shah SB, et al.
Pathophysiology associated with traumatic brain injury: Current treatments and potential novel therapeutics. Cell Mol Neurobiol 2017;37:571-85.
O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW, et al.
1,026 experimental treatments in acute stroke. Ann Neurol 2006;59:467-77.
Rosenfeld JV, Maas AI, Bragge P, Morganti-Kossmann MC, Manley GT, Gruen RL, et al.
Early management of severe traumatic brain injury. Lancet 2012;380:1088-98.
Chang JJ, Youn TS, Benson D, Mattick H, Andrade N, Harper CR, et al.
Physiologic and functional outcome correlates of brain tissue hypoxia in traumatic brain injury. Crit Care Med 2009;37:283-90.
Bouzat P, Sala N, Payen JF, Oddo M. Beyond intracranial pressure: Optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury. Ann Intensive Care 2013;3:23.
Ngwenya LB, Burke JF, Manley GT. Brain tissue oxygen monitoring and the intersection of brain and lung: A Comprehensive review. Respir Care 2016;61:1232-44.
Roh D, Park S. Brain multimodality monitoring: Updated perspectives. Curr Neurol Neurosci Rep 2016;16:56.
Price L, Wilson C, Grant G. Blood-brain barrier pathophysiology following traumatic brain injury. In: Laskowitz D, Grant G, editors. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016.
Valadka AB, Gopinath SP, Contant CF, Uzura M, Robertson CS. Relationship of brain tissue PO2 to outcome after severe head injury. Crit Care Med 1998;26:1576-81.
van den Brink WA, van Santbrink H, Avezaat CJ, Hogesteeger C, Jansen W, Kloos LM, et al.
Monitoring brain oxygen tension in severe head injury: The Rotterdam experience. Acta Neurochir Suppl 1998;71:190-4.
Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, et al.
Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017;80:6-15.
Czosnyka M. Increased intracranial pressure: What to do about it and when? Crit Care Med 2013;41:688.
Le Roux P. Physiological monitoring of the severe traumatic brain injury patient in the Intensive Care Unit. Curr Neurol Neurosci Rep 2013;13:331.
Chesnut RM, Temkin N, Carney N, Dikmen S, Rondina C, Videtta W, et al.
Atrial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 2012;367:2471-81.
Winkler EA, Minter D, Yue JK, Manley GT. Cerebral edema in traumatic brain injury: Pathophysiology and prospective therapeutic targets. Neurosurg Clin N Am 2016;27:473-88.
Rahmanian A, Haghnegahdar A, Rahmanian A, Ghaffarpasand F. Effects of intracranial pressure monitoring on outcome of patients with severe traumatic brain injury; results of a historical cohort study. Bull Emerg Trauma 2014;2:151-5.
Narotam PK, Morrison JF, Nathoo N. Brain tissue oxygen monitoring in traumatic brain injury and major trauma: Outcome analysis of a brain tissue oxygen-directed therapy. J Neurosurg 2009;111:672-82.
Radolovich DK, Czosnyka M, Timofeev I, Lavinio A, Kim DJ, Jaeger M, et al.
Transient changes in brain tissue oxygen in response to modifications of cerebral perfusion pressure: An observational study. Anesth Analg 2010;110:165-73.
Beynon C, Kiening KL, Orakcioglu B, Unterberg AW, Sakowitz OW. Brain tissue oxygen monitoring and hyperoxic treatment in patients with traumatic brain injury. J Neurotrauma 2012;29:2109-23.
van den Brink WA, van Santbrink H, Steyerberg EW, Avezaat CJ, Suazo JA, Hogesteeger C, et al.
Brain oxygen tension in severe head injury. Neurosurgery 2000;46:868-76.
Al-Rawi PG, Smielewski P, Kirkpatrick PJ. Evaluation of a near-infrared spectrometer (NIRO 300) for the detection of intracranial oxygenation changes in the adult head. Stroke 2001;32:2492-500.
Cruz SM, Akinkuotu AC, Rusin CG, Cass DL, Lee TC, Welty SE, et al.
Anovel multimodal computational system using near-infrared spectroscopy to monitor cerebral oxygenation during assisted ventilation in CDH patients. J Pediatr Surg 2016;51:38-43.
Kirkpatrick PJ, Lam J, Al-Rawi P, Smielewski P, Czosnyka M. Defining thresholds for critical ischemia by using near-infrared spectroscopy in the adult brain. J Neurosurg 1998;89:389-94.
Chen Q, Tan L, Chen Y, Liu X, Sun X, Feng H. The Importance of Monitoring and Curing in the “Silent Thirty-Nine Percent” of Patients with Severe Traumatic Brain Injury. Proc Neurosci 2016;1:29-34.
Mazzeo AT, Beat A, Singh A, Bullock MR. The role of mitochondrial transition pore, and its modulation, in traumatic brain injury and delayed neurodegeneration after TBI. Exp Neurol 2009;218:363-70.
Soane L, Kahraman S, Kristian T, Fiskum G. Mechanisms of impaired mitochondrial energy metabolism in acute and chronic neurodegenerative disorders. J Neurosci Res 2007;85:3407-15.
Barone DG, Czosnyka M. Brain monitoring: Do we need a hole? An update on invasive and noninvasive brain monitoring modalities. ScientificWorldJournal 2014;2014:795762.
Timofeev I, Carpenter KL, Nortje J, Al-Rawi PG, O'Connell MT, Czosnyka M, et al.
Cerebral extracellular chemistry and outcome following traumatic brain injury: A microdialysis study of 223 patients. Brain 2011;134:484-94.
Korde AS, Sullivan PG, Maragos WF. The uncoupling agent 2,4-dinitrophenol improves mitochondrial homeostasis following striatal quinolinic acid injections. J Neurotrauma 2005;22:1142-9.
Kristal BS, Stavrovskaya IG, Narayanan MV, Krasnikov BF, Brown AM, Beal MF, et al.
The mitochondrial permeability transition as a target for neuroprotection. J Bioenerg Biomembr 2004;36:309-12.
Qu J, Chen W, Hu R, Feng H. The injury and therapy of reactive oxygen species in intracerebral hemorrhage looking at mitochondria. Oxid Med Cell Longev 2016;2016:2592935.
Kozlov AV, Bahrami S, Calzia E, Dungel P, Gille L, Kuznetsov AV, et al.
Mitochondrial dysfunction and biogenesis: Do ICU patients die from mitochondrial failure? Ann Intensive Care 2011;1:41.
Azmoon S, Demarest C, Pucillo AL, Hjemdahl-Monsen C, Kay R, Ahmadi N, et al.
Neurologic and cardiac benefits of therapeutic hypothermia. Cardiol Rev 2011;19:108-14.
Bernard S. Hypothermia after cardiac arrest: Expanding the therapeutic scope. Crit Care Med 2009;37:S227-33.
Liu T, Zhao DX, Cui H, Chen L, Bao YH, Wang Y, et al.
Therapeutic hypothermia attenuates tissue damage and cytokine expression after traumatic brain injury by inhibiting necroptosis in the rat. Sci Rep 2016;6:24547.
Biswas AK, Bruce DA, Sklar FH, Bokovoy JL, Sommerauer JF. Treatment of acute traumatic brain injury in children with moderate hypothermia improves intracranial hypertension. Crit Care Med 2002;30:2742-51.
Ng HK, Hanel R, Freeman W. Prolonged mild-to-moderate hypothermia for refractory intracranial hypertension. J Vasc Interv Neurol 2009;2:142-6.
Polderman KH, Menon DK, Girbes AR. Treating intracranial hypertension in traumatic brain injury: Keep it cool! Intensive Care Med 2008;34:1738-9.
Sadaka F, Veremakis C. Therapeutic hypothermia for the management of intracranial hypertension in severe traumatic brain injury: A systematic review. Brain Inj 2012;26:899-908.
Andrews PJ, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JK, et al.
Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med 2015;373:2403-12.
Andrews PJ, Harris BA, Murray GD. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med 2016;374:1385.
Cooper DJ, Nichol A, Presneill J. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med 2016;374:1384.
Lazaridis C. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med 2016;374:1384.
Mayor S. Therapeutic hypothermia does not improve outcomes in traumatic brain injury, study finds. BMJ 2015;351:h5366.
O'Leary R, Hutchinson PJ, Menon D. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med 2016;374:1383-4.
Pines AR, Halasa TK, Sattur MG, Aoun RJ, Panchanathan R, Bendok BR, et al.
Hypothermia not supported as a therapeutic option for traumatic brain injury in recent randomized trial. World Neurosurg 2016;87:471-3.
Zhu Y, Yin H, Zhang R, Ye X, Wei J. Therapeutic hypothermia versus normothermia in adult patients with traumatic brain injury: A meta-analysis. Springerplus 2016;5:801.
Lopez GA. Temperature management in the neurointensive Care Unit. Curr Treat Options Neurol 2016;18:12.
Gu X, Wei ZZ, Espinera A, Lee JH, Ji X, Wei L, et al.
Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats. Exp Neurol 2015;267:135-42.
González CA, Rubinsky B. The detection of brain oedema with frequency-dependent phase shift electromagnetic induction. Physiol Meas 2006a; 27:539-52.
González CA, Rubinsky B. A theoretical study on magnetic induction frequency dependence of phase shift in oedema and haematoma. Physiol Meas 2006b; 27:829-38.
Gonzalez CA, Valencia JA, Mora A, Gonzalez F, Velasco B, Porras MA, et al.
Volumetric electromagnetic phase-shift spectroscopy of brain edema and hematoma. PLoS One 2013;8:e63223.
Griffiths H. Magnetic induction tomography. Meas Sci Technol 2001;12:1126.
Griffiths H, Stewart WR, Gough W. Magnetic induction tomography. A measuring system for biological tissues. Ann N Y Acad Sci 1999;873:335-45.
Tarjan PP, McFee R. Electrodeless measurements of the effective resistivity of the human torso and head by magnetic induction. IEEE Trans Biomed Eng 1968;15:266-78.
Foster KR, Schwan HP. Dielectric properties of tissues and biological materials: A critical review. Crit Rev Biomed Eng 1989;17:25-104.
Ruigang L, Ye L, Feng F, Fusheng Y, Xuetao S, Xiuzhen D. Time-difference imaging of magnetic induction tomography in a three-layer brain physical phantom. Meas Sci Technol 2014;25:065402.
Zolgharni M, Ledger PD, Armitage DW, Holder DS, Griffiths H. Imaging cerebral haemorrhage with magnetic induction tomography: Numerical modelling. Physiol Meas 2009;30:S187-200.
Zolgharni M, Griffiths H, Ledger PD. Frequency-difference MIT imaging of cerebral haemorrhage with a hemispherical coil array: Numerical modelling. Physiol Meas 2010;31:S111-25.
Qin M, Wang Y, Hu X, Jiao M, Liang W, Zhang H, et al
. Study of MIT phase sensitivity for detecting a brain edema based on FDTD method. The International Conference on Bioinformatics and Biomedical Engineering. IEEE;2007. p. 660-3.
Jiao M, Qin M, Liang W, Yang H, Wang W, Hu X, et al.
Design and implementation of a new type excitation source and the optimal excitation coil for MIT. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2009;26:234-8.
Liang W, Qin M, Jiao M, Yang H, Li K, Jiao T, et al
. Phase detection based on the lock-in amplifier SR844 and experiments of brain neuron cells in MIT system. International Conference on Biomedical Engineering and Informatics. May 27-30, 2008, Sanya, China. Available from: https://ieeexplore.ieee.org/document/4548747?arnumber=4548747
. [Last accessed on 2018 Dec 19].
Jin G, Qin M, Wang C, Guo W, Xu L, Ning X, et al
. Experimental study on simulated cerebral edema detection with PSSMI. Chin J Med Phys 2011;100:361-7.
Sun J, Jin G, Qin MX, Wan ZB, Wang JB, Wang C, et al.
Detection of acute cerebral hemorrhage in rabbits by magnetic induction. Braz J Med Biol Res 2014;47:144-50.
Sun J, Jin G, Li G, Chen Y, Qin M, Feng H. The experimental study of increased ICP on cerebral hemorrhage rabbits with magnetic induction phase shift method. Iran J Med Phys 2016;13:125-36.
Yang X, Zhao X, Yang K, Liu Y, Liu Y, Fu W, et al.
Biomedical applications of terahertz spectroscopy and imaging. Trends Biotechnol 2016b; 34:810-24.
Ji YB, Oh SJ, Kang SG, Heo J, Kim SH, Choi Y, et al.
Terahertz reflectometry imaging for low and high grade gliomas. Sci Rep 2016;6:36040.
Meng K, Chen TN, Chen T, Zhu LG, Liu Q, Li Z, et al.
Terahertz pulsed spectroscopy of paraffin-embedded brain glioma. J Biomed Opt 2014;19:077001.
Yamaguchi S, Fukushi Y, Kubota O, Itsuji T, Ouchi T, Yamamoto S, et al.
Brain tumor imaging of rat fresh tissue using terahertz spectroscopy. Sci Rep 2016a; 6:30124.
Lajevardipour A, Wood AW, McIntosh RL, Iskra S. Estimation of dielectric values for tissue water in the terahertz range. Bioelectromagnetics 2016;37:563-7.
Yamamoto N, Andachi T, Tamura A, Tominaga K. Temperature and hydration dependence of low-frequency spectra of lipid bilayers studied by terahertz time-domain spectroscopy. J Phys Chem B 2015;119:9359-68.
Yamaguchi S, Fukushi Y, Kubota O, Itsuji T, Ouchi T, Yamamoto S, et al.
Origin and quantification of differences between normal and tumor tissues observed by terahertz spectroscopy. Phys Med Biol 2016b; 61:6808-20.
Yang X, Wei D, Yan S, Liu Y, Yu S, Zhang M, et al.
Rapid and label-free detection and assessment of bacteria by terahertz time-domain spectroscopy. J Biophotonics 2016a; 9:1050-8.
Dielmann-Gessner J, Grossman M, Conti Nibali V, Born B, Solomonov I, Fields GB, et al.
Enzymatic turnover of macromolecules generates long-lasting protein-water-coupled motions beyond reaction steady state. Proc Natl Acad Sci U S A 2014;111:17857-62.
Murakami H. Protein and water confined in nanometer-scale reverse micelles studied by near infrared, terahertz, and ultrafast visible spectroscopies. Adv Protein Chem Struct Biol 2013;93:183-211.
White TE, Ford BD. Gene interaction hierarchy analysis can be an effective tool for managing big data related to unilateral traumatic brain injury. In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015.
Ou S, Liu GD, Zhou LS, Xia X, Bai SR, Li J, et al.
Bioinformatics analysis of gene expression profiles in the rat cerebral cortex following traumatic brain injury. Eur Rev Med Pharmacol Sci 2014;18:101-7.
Feala JD, Abdulhameed MD, Yu C, Dutta B, Yu X, Schmid K, et al.
Systems biology approaches for discovering biomarkers for traumatic brain injury. J Neurotrauma 2013;30:1101-16.
Guingab-Cagmat JD, Cagmat EB, Hayes RL, Anagli J. Integration of proteomics, bioinformatics, and systems biology in traumatic brain injury biomarker discovery. Front Neurol 2013;4:61.
Sharma P, Su YA, Barry ES, Grunberg NE, Lei Z. Mitochondrial targeted neuron focused genes in hippocampus of rats with traumatic brain injury. Int J Crit Illn Inj Sci 2012;2:172-9.
] [Full text]
White TE, Ford GD, Surles-Zeigler MC, Gates AS, Laplaca MC, Ford BD, et al.
Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response. BMC Genomics 2013;14:282.
Yu C, Boutté A, Yu X, Dutta B, Feala JD, Schmid K, et al.
Asystems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury. J Neurosci Res 2015;93:199-214.
Kilbaugh TJ, Lvova M, Karlsson M, Zhang Z, Leipzig J, Wallace DC, et al.
Peripheral blood mitochondrial DNA as a biomarker of cerebral mitochondrial dysfunction following traumatic brain injury in a porcine model. PLoS One 2015;10:e0130927.
Livesay SL. The bedside nurse: The foundation of multimodal neuromonitoring. Crit Care Nurs Clin North Am 2016;28:1-8.
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