Diffuse Axonal Injury Imaging 

Diffuse axonal injury (DAI) is a frequent result of traumatic deceleration injuries and a frequent cause of persistent vegetative state in patients. In fact, DAI represents approximately one half of all intra-axial traumatic lesions.^[1] This lesion is the most significant cause of morbidity in patients with traumatic brain injuries, which most commonly result from high-speed motor vehicle accidents. DAI typically consists of several focal white-matter lesions measuring 1-15 mm in a characteristic distribution. See the images below.

Classically, DAI has been considered a primary-type injury, with damage occurring at the time of the accident. Research has shown that another component of the injury comprises the secondary factors (or delayed component), since the axons are injured, secondary swelling occurs, and retraction bulbs form. Of patients with DAI, 80% demonstrate multiple areas of injury on computed tomography (CT) scans.

The degree of microscopic injury usually is considered to be greater than that seen on diagnostic imaging, and the clinical findings reflect this point. DAI is suggested in any patient who demonstrates clinical symptoms disproportionate to his or her CT-scan findings. DAI results in instantaneous loss of consciousness, and most patients (>90%) remain in a persistent vegetative state, since brainstem function typically remains unaffected. DAI rarely causes death.

Preferred Examination

Magnetic resonance imaging (MRI) is the preferred examination for DAI (particularly with gradient-echo sequences), although CT scanning may demonstrate findings suggestive of DAI and is more practical and available.^{[2, 3, 4, 5]} Studies have indicated that MRI can play a role in predicting the length of coma in DAI patients. However, MRI is contraindicated in patients with implanted pacemakers or certain types of metallic prostheses, as well as in patients who have metallic foreign bodies, such as bullet fragments, in their head or neck or near important vascular structures. In addition, MRI is difficult to perform on patients who have claustrophobia and on ventilator-dependent patients.

No specific findings related to DAI can be made using conventional radiography, the degree of confidence is low, as conventional radiography cannot demonstrate subtle soft-tissue changes; however, other signs of head trauma can be appreciated, such as facial bone fractures or fluid levels within the paranasal sinuses. Radiographs can also clearly demonstrate skull fractures, but this is not helpful in DAI, as DAI is rarely associated with skull fracture. Thus, many false negatives are possible, because a negative skull radiograph in no way excludes a parenchymal brain injury.

Among patients eventually proven to have DAI, 50-80% demonstrate a normal CT scan upon presentation. Delayed CT scanning may be helpful in demonstrating edema or atrophy, which are later findings. Small petechial hemorrhages located at the gray-white matter junction (as seen in the image below), as well as in the corpus callosum and brainstem, are characteristic of CT-scan findings in the acute setting.

Wang and colleagues^[6] suggested CT scan criteria using the presence of one or more small intraparenchymal hemorrhages less than 2 cm in diameter located in the cerebral hemispheres, intraventricular hemorrhage, hemorrhage in the corpus callosum, small focal areas of hemorrhage less than 2 cm in diameter adjacent to the third ventricle, and brainstem hemorrhage as characteristic of DAIs. There may also be small focal areas of low density on CT scans; these correspond to areas of edema occurring where shearing injury took place.

The degree of confidence in CT scanning is moderate, as the only finding may be petechial hemorrhage, and fewer than 20% of patients with DAI demonstrate this finding on CT scanning alone. When petechial hemorrhages are observed with the appropriate clinical findings, the sensitivity of CT scanning in the detection of DAI is high.

As with conventional radiographs, frequent false negatives are possible, because normal or almost normal CT-scan findings are common in patients with DAI on initial presentation, as demonstrated in the image below. For this reason, when CT-scan findings are negative and DAI is suggested clinically, MRI may be performed, as MRI modality can demonstrate lesions not observed through CT scanning. However, although MRI is more sensitive in the detection of subtle soft-tissue abnormalities, CT scanning is more available and practical in the current medical environment and is therefore, according to Teasdale, the "mainstay of acute investigation of head injury."^[7]

Recommended MRI sequences include T1-weighted, T2-weighted, T2–gradient-echo, proton density–weighted, and diffusion-weighted images.^[8] The degree of confidence is high, as abnormal signal in the characteristic locations, discovered in the clinical setting of recent trauma, leaves little doubt about the diagnosis of DAI. In a prospective cohort study, Skandsen et al examined MRI scans from patients in the early phase of moderate to severe head injury and determined the prognosis was better in patients with DAI whose lesions were confined to the lobar white matter or who had callosal lesions than it was in patients with DAI who had lesions in the dorsolateral brainstem.^[9]

T1-weighted images are helpful for anatomic localization^[10] ; however, nonhemorrhagic lesions may be isointense to surrounding tissue. Hemorrhagic lesions appear hyperintense on T1-weighted images. However, on T2-weighted sequences, nonhemorrhagic lesions appear hyperintense. Diffusion-weighted sequences can reveal hyperintensities in areas of axonal injury.

As demonstrated in the image below, gradient-echo sequences are particularly useful in revealing the paramagnetic effects of petechial hemorrhages. Gradient-echo imaging can often show signal abnormality in areas that appear normal in T1- and T2-weighted spin-echo sequences. For this reason, gradient-echo imaging has become a mainstay of MRI exams for patients with suggested shearing-type injuries. The abnormal signal on gradient-echo images can persist for many years after the injury.

The most common MRI finding of DAI, as seen in the image below, is the presence of multifocal areas of abnormal signal (bright on T2-weighted images) at the white matter in the temporal or parietal corticomedullary junction or in the splenium of the corpus callosum. Other areas that frequently are abnormal include the dorsolateral rostral midbrain and the corona radiata. Eventually, nonspecific atrophic changes are observed.

One area of research has been magnetization transfer imaging. Studies have reported that the magnetic transfer ratio has shown promise in identifying areas of injury not visible on the above MRI pulse sequences. This may allow the radiologist to appreciate a truer representation of the degree of microscopic injury. Studies have also indicated that MRI can play a role in predicting the length of coma in DAI patients. The volume of white-matter lesions has been correlated to the degree of injury, as measured by MRI.^[11] MRI has also been used to quantify cerebral blood flow in damaged areas of the brain, thus predicting injury severity.

In a study of 11 patients with DAI, Sugiyama et al employed voxel-based analysis to investigate the clinical usefulness of diffusion tensor imaging (DTI) and found significantly more brain regions with decreased fractional anisotropy (FA) were found on the DTI scans of patients with DAI than on those of control subjects.^[12] In addition, DTI revealed more brain lesions than did conventional MRI. The authors also found that patients' cognitive scores on functional independence and functional assessment measures correlated with the number and size of DAI lesions. Moreover, fiber tractography–based analysis revealed that DAI patients with memory disorders exhibited an interruption of fibers within the fornix. According to Sugiyama and colleagues, their data indicated that DTI is an effective modality for detecting lesions and examining cognitive disorders in patients with DAI.^[12]

Multiple sclerosis (MS) is a progressive neurologic disorder that can involve multiple foci of white-matter signal abnormality on MRI; however, MS lesions typically are oval or oblong and are oriented in a direction perpendicular to the border of the lateral ventricles (Dawson fingers). In addition, MS lesions may involve the spinal cord, a finding not associated with DAI, and the clinical course of MS is dramatically different from that of DAI.

False negatives may occur with MRI if only routine sequences are performed. A sequence (such as gradient echo) that accentuates the susceptibility artifact arising from blood products must be performed in order to recognize small petechial hemorrhages.

Nuclear medicine currently has no role in the routine diagnostic workup of patients with possible DAI; however, studies have suggested that iodine-123 (¹²³ I) single-photon emission CT (SPECT) imaging demonstrates areas of hypoperfusion in areas of known injury and reveals additional areas of injury not visualized with MRI.