Introduction
Head injury is a leading cause of disability and death in adults, and most patients (85–95%) are classified as having a mild-to-moderate head injury. (Hassan, 2005) Most of these patients recover within weeks to months without specific therapy. However, a subgroup continues to experience disabling symptoms that interfere with their return to work or resumption of social activities. The burden of these symptoms is not only personal but also socioeconomic, as they are most common in young patients in their 20s and 30s with full occupational status. It is of paramount importance to identify those patients who are prone to develop cognitive disability to promote early rehabilitation. (George, 2002)
In recent decades, major advances in the development of imaging techniques have contributed to the knowledge of the pathophysiology of head injury. The capabilities of structural imaging have been expanded by various techniques suitable for visualizing hemodynamic and metabolic changes in the brain. Concurrently, the treatment of patients with trauma is increasingly guided by the rapid assessment of primary damage and prevention of further deterioration. Hence, selection of the technique most valuable in guiding management during the acute phase of injury is essential, as is the assessment of the additional value of the technique in predicting outcome.
In this article, we present an overview of the current imaging techniques in terms of their ability to reveal structural or functional brain abnormalities in patients with a head injury. We focus on patients with a mild-to-moderate head injury, defined by a Glasgow coma score of more than 8, as most patients sustain this type of head injury and, in contrast to severe head injury, scarce information is available on this topic. As some extensive reviews of imaging studies in children are already available, this review focuses on studies of mild-to-moderate head injury in adults. We discuss the advantages and limitations of various techniques for the initial assessment and identification of brain abnormalities and their role in the prediction of outcomes.
Structural imaging
In traumatic brain injury, the mechanism of damage can be classified as primary and secondary. In general, structural imaging techniques are used to visualize primary brain injury. Primary brain injury occurs at the moment of impact, with diffuse axonal injury being the most important primary lesion. Diffuse axonal injury is a consistent finding in mild, moderate, and severe traumatic head injury, although the severity increases with that of the head injury.
Primary brain injury also comprises focal abnormalities, such as contusions and hematomas, as a result of either direct external contact forces or from the movement of the brain within the skull. Secondary brain injury, on the other hand, develops within hours after impact as a result of primary injury and mainly consists of ischemia; this is best visualized using functional imaging. (Munson, 2006) In the emergency setting, clinical management is guided by the imaging of structural abnormalities requiring acute interventions. (LoBiondo-Wood, 2005) During follow-up, structural imaging techniques are most commonly used to explain post-concussional symptoms or to predict the outcome. Structural imaging techniques in patients include CT and MRI.
CT
CT is one of the first developed and most commonly applied imaging techniques in the acute phase of head injury and can be used to detect hemorrhage, parenchymal injury, and skull fractures. CT is the most relevant imaging procedure for the detection of lesions eligible for surgical intervention, as it is rapidly and easily done, even in agitated patients.
For mild and moderate head injury, there is no agreement about routine CT scanning. There is substantial variation among institutions in the ordering of CT for patients with a mild head injury, ranging from 16% to 74%. When all patients with mild-to-moderate head injury are scanned, the incidence of abnormal findings is about 15%, increasing to 50% when a CT scan is done in only those patients with neurological symptoms.
However, the absence of focal neurological abnormalities on physical examination does not rule out CT abnormalities. Since the introduction of the UK National Institute for Health and Clinical Excellence guidelines for the management of head injury, the use of CT has substantially increased, and the reported incidence of intracranial abnormalities is about 10%. (Wardlaw, 2002) A low Glasgow coma scale, the presence of a skull fracture, old age, and focal neurological signs are associated with a higher incidence of abnormal CT findings in patients with a mild head injury.
The overall sensitivity of CT to abnormalities in acute head trauma is 63–75%. (LoBiondo-Wood, 2006) In patients with a mild-to-moderate head injury, edema or lesions on CT are related to problems with the resumption of work. Also, the presence of subarachnoid blood on CT is a significant predictor of outcome. Contusions in frontal and temporal lobes, when present on CT, result in relevant deficits in outcome caused by behavioral and cognitive problems. Lesion size is inversely associated with outcome. Furthermore, about 20% of patients who sustain mild-to-moderate head injury without abnormalities on the admission CT have problems with resuming work, suggesting that the conventional CT scan has limited ability in detecting structural and functional abnormalities.
MRI
MRI is the technique of choice in the subacute phase of head injury and during follow-up. The difficulty of using MRI to evaluate skull fractures, the limitations in monitoring patients during MRI, and the susceptibility to motion artifacts related to the relatively long exposure time discourage the use of this technique in the acute phase of head injury. Although in earlier studies MRI was inferior to CT in the detection of parenchymal and subarachnoid hemorrhages, MRI is now as reliable as CT in detecting these hemorrhages in the acute phase because of improvements in MRI techniques. Moreover, MRI is more sensitive than CT in detecting diffuse axonal injury and non-hemorrhagic contusions, especially in the frontal and temporal regions at the base of the skull. MRI is also more sensitive in detecting small subdural hematomas and brainstem injury.
A third of patients with mild-to-moderate head injury have focal atrophy in the frontal and temporal regions on MRI in the chronic phase, which is predictive of outcome. (Munson, 2006) In addition to whole-brain atrophy, the number, size, and depth of lesions are also associated with the degree of unconsciousness and outcome. Serial MRI scanning showed a resolution of lesions as well as simultaneous improvement on neuropsychological testing. (Hassan, 2005)
In summary, structural imaging techniques, such as conventional CT and MRI, depict primary traumatic brain injury. The timing of imaging is important as information provided by CT imaging is most appropriate early in the course of injury and MRI methods are more helpful in the recovery phase. However, conventional CT and MRI have a limited negative predictive value, as the absence of abnormalities is no guarantee of optimum outcome. (Wardlaw, 2002)
The first results of MRI modalities based on diffusion methods, such as diffusion-weighted imaging and diffusion tensor imaging, in head injury are promising. As diffusion-based methods indirectly rely on the energy status of the cells, these techniques could provide information on the secondary injury. (LoBiondo-Wood, 2005) Further investigation is needed, especially in patients with a mild-to-moderate head injury. Because conventional CT and MRI cannot show functional cerebral changes and therefore secondary brain injury, functional imaging techniques might be of more value in predicting outcomes.
Functional imaging
Functional imaging techniques are used to measure hemodynamic or metabolic changes in the brain, mainly in the subacute phase of injury when a secondary injury is developing. Secondary brain damage mainly consists of ischemia and is present in more than 80% of fatal cases of head injury. Even in monitored patients, ischaemic damage occurs. In a series of patients with differing severity of the head injury, 92% had one or more ischaemic insults lasting for at least 5 min, despite being monitored in a well-equipped intensive-care unit. (Hassan, 2005)
Functional imaging studies include hemodynamic imaging such as single-photon emission computed tomography (SPECT) and PET, although the latter technique also provides information on the metabolic status of the brain. Although xenon-CT was one of the first techniques used to examine perfusion in patients with a head injury, information is available mainly on severe head injury and as such is not relevant to this review. (Hoeffner, 2004) Imaging techniques such as perfusion MRI and perfusion CT are described, in which hemodynamic imaging is added to a modality originally used for structural imaging, thereby expanding the possibilities for the visualization of brain abnormalities. (Munson, 2006)
Advanced MRI techniques such as functional MRI and magnetic resonance spectroscopy (MRS) provide information on the metabolic state of the brain with the former combining the accuracy of MRI with information on activation patterns of localized brain functions and the latter providing information on the metabolic state of the brain. (Newberg, 2003)
SPECT
SPECT is a procedure that provides an indirect indicator of brain metabolism by measuring cerebral blood flow.8 Several radiotracers are available, with 99mTc-hexamethyl propylene amine oxide (HMPAO) being the most common. In 40–70% of patients with a mild-to-moderate head injury, abnormal SPECT findings are observed, especially within the first 3 months of injury. (Newberg, 2003) Most of these patients have areas of hypoperfusion, predominantly located in their frontal and temporal lobes, basal ganglia, and thalami. Hypoperfusion seen on SPECT imaging correlates with the duration of post-traumatic amnesia after mild head injury. (Hoeffner, 2004)
Also, hypoperfusion on SPECT imaging is shown to be correlated with loss of consciousness and postconcussional syndrome. In symptomatic patients with a long-standing mild traumatic head injury and unremarkable structural brain imaging, reduced CBF is seen on SPECT imaging, concordant with neuropsychological testing. A negative initial SPECT study is a reliable predictor of a favorable clinical outcome at 3 months after mild head injury. (LoBiondo-Wood, 2005)
In general, HMPAO SPECT seems to be more sensitive than CT or MRI in the detection of brain abnormalities in patients with a mild-to-moderate head injury, with a larger area of involvement on SPECT than on CT. However, the greater number of articles describing the use of SPECT than any other technique in mild traumatic brain injury does not indicate that it is more sensitive because its application is still limited by its poor resolution, radiation exposure, and difficulty in obtaining quantitative data.
Perfusion MRI
Perfusion-weighted imaging, in which hemodynamically weighted MRI sequences are based on the passage of a contrast agent through the brain, is sensitive to microscopic tissue-level changes in cerebral blood volume, and parameters like cerebral blood volume, mean transit time, and cerebral blood flow can also be obtained. George did a perfusion MRI study in the subacute phase of head injury and found low cerebral blood volume in regions of focal pathology in patients with contusions and edema visible on conventional MRI. In addition, there was one group of patients who had reduced cerebral blood volume in a normal-appearing brain. (Munson, 2006)
These patients had a significantly worse clinical outcome than patients without abnormalities on perfusion MRI. Furthermore, these measurements were present on average 10 days after the injury, implying that delayed changes in hemodynamic parameters, and not just acute changes, may be involved in determining clinical outcome. (George, 2002)
An important limitation of this technique is that quantification remains difficult, together with limited application in the emergency setting. Furthermore, the use of a contrast agent is needed, unless the more recently developed spin-labeling technique is used.
Perfusion CT
Perfusion CT data are obtained by monitoring the first pass of an iodinated contrast agent bolus through cerebral vasculature. Investigators can then calculate parameter maps of cerebral blood volume, mean transit time, and cerebral blood flow, and the use of regions of interest allows quantification of perfusion in the brain. In recent years, the broad introduction of fast multidetector CT systems and the development of commercially available software for perfusion analysis have facilitated the application of cerebral perfusion imaging in the clinical setting. (Wardlaw, 2002)
After first being used in patients with stroke, this technique is gradually being used in those with a head injury. Perfusion CT features specific patterns in the acute phase related to outcome in patients with a severe head injury. Normal brain perfusion or hyperemia is seen in patients with favorable outcomes and oligaemia is seen in patients with unfavorable outcomes. (Newberg, 2003) Perfusion CT is more sensitive than conventional unenhanced CT in the detection of cerebral contusions, featured as areas with lowered cerebral blood flow and cerebral blood volume and increased mean transit time. (Hassan, 2005)
Also, in the first study of head injury in children and patients with a mild-to-moderate head injury, there were comparable abnormalities. Perfusion CT values of cerebral blood volume were lower near epidural or subdural hematomas. Apart from advantages such as low exposure time and 24 h availability in most hospitals, use is limited by partial brain coverage and radiation exposure. (Munson, 2006) The promising potential of perfusion CT in the detection of secondary ischaemic changes in the acute phase of head injury is unproven in mild-to-moderate head injury.
PET
Several studies have investigated the use of PET for the assessment of patients with head trauma. PET provides tomographic images of quantitative parameters describing various features of brain hemodynamics, including cerebral blood flow, cerebral blood volume, oxygen extraction fraction, and cerebral metabolic rate of oxygen. The most frequently used PET tracer is fluorine-18 labeled fluorodeoxyglucose (FDG) for the detection of regional glucose consumption. (Hoeffner, 2004)
PET studies generally show cerebral dysfunction beyond the structural abnormalities demonstrated by CT and MRI. About a third of these anatomical lesions are associated with more widespread metabolic abnormalities, and as much as 42% of PET abnormalities were not associated with any anatomical lesions. Epidural and acute subdural hematomas cause an extensive reduction in metabolism in both the involved adjacent cortex and the corresponding contralateral cortex. Diffuse axonal injury causes widespread hypometabolism, predominantly in the parieto-occipital cortex. The period of metabolic reduction typically persists for several weeks regardless of injury severity. (George, 2002)
In the acute phase of mild head injury, a normal FDG-PET but an abnormal frontoparietal cortical brain perfusion was found using SPECT. This suggests that edema and vasospasm secondary to mild traumatic brain injury cause decreased perfusion detected by SPECT, but that it is not severe enough to impair glucose uptake. In patients with a mild-to-moderate head injury, a good correlation between the severity of the injury as measured by the Glasgow coma scale and the extent of whole-brain metabolism was demonstrated, especially in patients with a score of 13 or lower.
In the chronic phase after the mild head injury, there are inconsistencies in PET findings varying from regional hypometabolism to global hypermetabolism. Scheibel and colleagues found no difference in cerebral FDG uptake between patients with mild head injury and controls in the resting state. In patients with mild-to-moderate head injury with postconcussive symptoms, there is a correlation between complaints and the number of PET metabolic abnormalities, although both hypometabolism and hypermetabolism were seen in the same regions across different patients with a mild head injury. (Scheibel, 2007)
In patients with a mild head injury and postconcussive symptoms, a high incidence of temporal lobe injury is visible on FDG-PET, with a good association between PET abnormalities and neuropsychological assessment. Global and regional metabolic rates improve as patients clinically recover from head trauma. (Munson, 2006)
Besides glucose metabolism, information from PET imaging of cerebral blood flow in patients with a head injury is also obtained with oxygen-15 labeled H2O, CO, and O2 tracers. Information on patients with a mild or moderate head injuries is scarce. Soeda and colleagues showed that a large ischaemic brain volume was associated with a poor outcome as measured with the Glasgow outcome score 6 months after injury. (Soeda, 2007)
In addition, a PET study of patients with a moderate-to-severe head injury revealed the use of altered functional neuroanatomical networks when performing memory tasks, whereas patients with mild head injury had a small increase in cerebral blood flow in the right prefrontal cortex, compared with that in healthy people, during a memory task. (Hassan, 2005)
Although quantitative data can be obtained with PET and it offers a better resolution than SPECT, the application of this technique is limited by radiation exposure and scarce availability due to high costs. It is mainly used as a research tool in a non-emergency setting.
MRS
MRS offers a unique approach for assessing the metabolic status of the brain in vivo. In particular, this technique provides a non-invasive means for quantifying numerous metabolites such as N-acetyl aspartate, creatine, choline, and lactate. Of particular importance is N-acetyl aspartate, because it is considered a marker of neuronal injury or loss. N-acetyl aspartate is found to be decreased in cerebral contusions and the corpus callosum. N-acetyl aspartate concentrations in grey matter were predictive of overall neuropsychological ability in patients with a moderate-to-severe head injury.
Moreover, an N-acetyl aspartate/choline ratio is related to injury severity and outcome even when white matter appears normal on MRI. (Hoeffner, 2004) and colleagues showed that in patients with a mild head injury the N-acetyl aspartate/creatine ratio was low in areas of pericontusional edema. Moreover, the lactate/creatine ratios were high in these areas, suggestive of ischaemic damage. Patients with good recovery, as measured with the Glasgow outcome score, have high N-acetyl aspartate/creatine ratios. (LoBiondo-Wood, 2006) Despite these positive results, other researchers have found no associations between metabolic ratios and outcome at 6 months in individuals with a mild head injury.
Choline, a marker for cell membrane disruption and inflammation, was high in the normal-appearing frontal white matter, grey matter, and parieto-occipital white matter. Soeda and colleagues showed that increased choline concentrations in grey matter were not related to the neuropsychological outcome at 6 months postinjury, contrary to another MRS study that revealed that a high choline concentration in both white and grey matter at 3 months after injury was significantly related to poorer outcome. (Soeda, 2007)
Although MRS provides a rapid way to assess in vivo brain composition, the interpretation of results is hindered by reliance upon ratios in various brain regions. Furthermore, the technique has a poor resolution and only partial brain coverage, and its use is limited in the acute phase of head injury.
Functional MRI
Functional MRI is a non-invasive technique in which blood-oxygen changes serve as an endogenous contrast agent. Most current functional MRI studies are based on the blood-oxygen-level-dependent (BOLD) method, in which the signal is derived from local changes in the ratio of deoxygenated to oxygenated hemoglobin that accompanies neuronal events. Deoxyhaemoglobin and oxyhemoglobin differ in their magnetic properties, so the changes in their relative proportions result in a temporary change in the magnetic resonance signal of the target region relative to surrounding tissue.
Functional MRI is a promising technique because it combines the anatomical precision of MRI with functional information. Activation of brain regions involved in a particular language or cognitive task can be mapped, thereby increasing our knowledge of neuropsychological dysfunction. (Munson, 2006) To date, standardized imaging protocols for functional MRI have been developed mainly for the assessment and visualization of brain regions involved in cognition and behavior. In severe head injury, functional MRI displays a more regionally dispersed pattern of cerebral activation, lateralized to the right hemisphere. (George, 2002)
In a study on head injuries of varying severity, there were changes in brain activation, suggesting that altered neural networks mediate cognitive control after the head injury, possibly as a result of diffuse axonal injury. In patients with pure diffuse axonal injury, compensatory activation of the prefrontal region was seen in comparison to healthy controls.
Hoeffner used functional MRI in patients with a mild-to-moderate head injury to probe working memory function (ie, the ability to retain information and to manipulate it in reaction to newly incoming material) within about 1 month of injury and in some cases 1 year later. Patients with head injury differed from control individuals in the activation pattern of working memory circuitry, with significantly higher activation on functional MRI during moderate working memory load conditions, especially in the parietal and prefrontal regions. (Hoeffner, 2004)
Task performance did not differ between patients and controls, suggesting that injury-related changes to modulating working memory might underlie some of the memory complaints after mild head injury. In a study of concussed athletes with a mild head injury, patients had low activation in the right prefrontal cortex compared with healthy controls on a memory task. However, football players have larger amplitude and more extensive activation patterns, predominantly in parietal, lateral frontal, and cerebellar regions, after a motor sequencing task in the absence of a decline in neurobehavioural performance. (Hassan, 2005)
Functional MRI is a promising diagnostic imaging method for the assessment of cognitive, task-related dysfunction in the chronic phase after head injury. Functional MRI has the advantage over imaging techniques such as PET and SPECT because multiple sessions can be done on a single patient in a short period. These features promote prospective studies with baseline measures of neurological function. Furthermore, functional MRI holds great potential for widespread research and clinical use because it does not require exposure to ionizing radiation. The application of this technique is best in the chronic phase when the patient is cooperative and able to comprehend test instructions.
New techniques
Magnetoencephalography is a new technology that is based on the detection of magnetic field potentials and permits real-time direct assessment of brain electrophysiology. Magnetoencephalography is superior to standard electroencephalography as it provides more precise temporal and spatial patterns that are free from artifacts. The source of the electroencephalography abnormality can be localized by magnetoencephalography and registered on a standard MRI. As such, this technique is not a common imaging technique but provides a combination of a measure of electrophysiological dysfunction with anatomical information.
Magnetoencephalography technology is used as a clinical diagnostic procedure for epilepsy and experimental research on sensorimotor and language function. It also provides useful information for the assessment of cognitive complaints. In a study of head injury patients with postconcussive symptoms, the combined use of magnetoencephalography and MRI resulted in the detection of abnormal activity in 65% of patients compared with 10% in asymptomatic patients. The level of functional damage in patients with head injuries far exceeds the area of focal damage depicted with structural imaging. To date, clinical studies with magnetoencephalography are limited and it is too early to draw any conclusions relating to its potential use in head injury. (LoBiondo-Wood, 2005)
Additional limitations for its use in a routine setting include costs and specialized requirements for housing these systems as a result of the need to shield the magnetic noise.
In summary, functional imaging techniques depict more and larger areas of abnormalities than do structural imaging techniques in patients with a head injury. Although functional imaging in patients with a severe head injury is of prognostic value, there are little data from patients with a mild-to-moderate head injury.
Conclusions
We have assessed various structural and functional imaging techniques in a clinical setting to guide management and to provide prognostic information on mild-to-moderate head injury. General problems that apply to imaging in patients with mild-to-moderate head injury are the heterogeneity of the population in terms of the extent, type, and location of the injury. A distinction has to be made between management in the acute phase after injury when the varying cooperation in agitated or confused patients interferes with rapid assessment and the investigation of symptoms and abnormalities in the chronic phase.
In the management of head injury, conventional CT is the imaging modality of the first choice in the acute phase. CT is the most relevant imaging procedure for the detection of lesions eligible for surgical intervention, and it is rapidly and easily done. However, a normal CT on admission does not preclude brain injury and is of limited prognostic value. Although MRI is superior to CT in detecting diffuse axonal injury and non-hemorrhagic contusions, this technique is not easily applicable in the acute phase of head injury owing to the limitations in the monitoring of patients during MRI and the susceptibility to motion artifacts related to the long exposure time.
Furthermore, there is no evidence that additional MRI affects neurosurgical management in patients with a head injury. In general, within 1–3 months after injury, MRI assessment is preferable to other approaches if the appropriate sequences are used for the detection of post-traumatic abnormalities. Recently developed MRI techniques such as diffusion-weighted imaging and diffusion tensor imaging are promising as they provide more insight into the pathophysiological mechanisms of head injury. However, their prognostic value is unknown.
Functional imaging can provide useful information for determining the extent of ischaemic and metabolic injury in patients with a head injury. The main imaging techniques dedicated to brain hemodynamics and metabolism in head injury are MRS, functional MRI, SPECT, and PET. In general, SPECT and PET seem to be more sensitive in lesion detection compared with structural imaging techniques such as CT and MRI. Both imaging techniques have limited availability and are mainly used in a research setting. MRS and functional MRI combine the accuracy of MRI with information on brain function and the metabolic state of the brain and are preferably used in the chronic phase after injury.
The use of perfusion MRI and perfusion CT is not extensively investigated in traumatic head injury. Perfusion MRI provides better brain coverage than does perfusion CT, although this latter technique has some promising qualities, despite its radiation exposure, as it has a low exposure time and is readily available in most emergency departments. If it becomes more readily available, magnetoencephalography might be a promising neuroimaging technique in the future. This new technique provides anatomical information that can be related to neuropsychological and neurobehavioural outcomes.
New technologies adding a functional dimension to structural imaging are likely to improve the relationship between neuroimaging and outcome as they provide an index of hemodynamic and metabolic function in addition to anatomy. Additional studies are needed to assess the extent and duration of abnormalities found in symptomatic and asymptomatic patients. The potential ability of new MRI techniques to visualize axonal injury as the major pathological substrate of traumatic brain injury is promising. The ability of functional neuroimaging to depict brain activity during cognitive tasks will enable the possibility to determine the efficacy of various rehabilitation programs.
Further studies of mild-to-moderate head injury are necessary to prove the feasibility of neuroimaging for this patient group, as management is increasingly directed by the demand for imaging techniques that provide information to guide clinical management and help to determine prognosis.
References
George, G (2002) Nursing Theories : The Base for Professional Nursing Practice (5th ed) Prentice Hall.
LoBiondo-Wood, G & Haber, J. (2006) Nursing Research – Methods and Critical Apprasal for Evidence _ Based Practice (6 th ed) Elsevier : St. Louis, Missouri.
Munson S, Schroth E and Ernst M, (2006) The Role Of Functional Neuroimaging In Pediatric Brain Injury, Pediatrics 117, pp. 1372–1381.
Hassan Z, Smith M and Littlewood S et al., (2005) Head Injuries: A Study Evaluating The Impact Of The Nice Head Injury Guidelines, Emerg Med J 22, pp. 845–849.
Wardlaw JM, Easton VJ and Statham P, (2002) Which CT Features Help Predict Outcome After Head Injury?, J Neurol Neurosurg Psychiatry 72, pp. 188–192.
Newberg AB and Alavi A, (2003) Neuroimaging In Patients With Head Injury, Semin Nucl Med 33, pp. 136–147.
Hoeffner EG, Case I and Jain R et al., (2004) Cerebral Perfusion CT: Technique And Clinical Applications, Radiology 231, pp. 632–644.
Soeda A, Nakashima T and Okumura A et al., (2005) Cognitive Impairment After Traumatic Brain Injury: A Functional Magnetic Resonance Imaging Study Using The Stroop Task, Neuroradiology 47 (2005), pp. 501–506.
Scheibel RS, NewsomMR e and Steinberg JL et al., (2007) Altered Brain Activation During Cognitive Control In Patients With Moderate To Severe Traumatic Brain Injury, Neurorehabil Neural Repair 21, pp. 36–45.