With the development of emergency and intensive medical technologies, the survival rate of craniocerebral injury has greatly improved. Accordingly, much more patients with severe coma have been converted from severe coma to alleviated state of consciousness, which can be subsequently classified within the framework of disorders of consciousness (DOC) in variety of degrees [1]. The morbidity of DOC patients in China is over than 100,000 per year, associated an expenditure up to 30-50 billion yuan in health care. It leads to conflict social controversy related to economic and ethical issues [2].

DOC can be classified into different levels including unresponsive wakefulness syndrome (UWS) and Minimally conscious state (MCS). UWS refers to a patient who is unresponsive to external stimuli with wakefulness state (with open eyes) [3]. MCS refers to the patient with detectable signs of fluctuation in consciousness and repeatable non-reflex behavior [4]. Until now, the clinical diagnosis of DOC mainly depends on grading scales, such as Coma Recovery Scale-Revised (CRS-R) and Glasgow Coma Scale (GCS). Studies have shown that the misdiagnosis rate is as high as 43% between UWS and MCS relying on those diagnostic and evaluating methods [5]. This is mainly due to common concealment behaviors of DOC patients and the impact of the subjectivity of factors in the evaluation, which in turn results in inter-observer variability. Luaute et al [6] showed that the long-term recovery of MCS patients was better than that of UWS patients. Therefore, it is very important to select an appropriate and sensitive evaluating method for the early identification of these two status.

Diffusion tensor imaging (DTI) technology is an practical method for detecting subtle changes in brain structure; it is also a non-invasive method to observe the integrity of the tissue structure in vivo and obtain the information of fiber track, such as morphology, directions and myelin changes, in cerebral white matter [7, 8]. The present study had applied DTI technology to scan the selected regions of interest (ROIs) (brainstem, subcortex, and thalamus) in UWS and MCS patients individually, in the purpose of obtaining the values of FA and MD, as an indicator of conscious level evaluation. The differences between the two groups were compared to investigate the variations in mean values of various indicators for patients in different consciousness levels. The correlation between the parameters in different ROIs and the CRS scores is expected to have a further exploration of the clinical applications of DTI technology in the diagnosis and grading of DOC.

The morbidity of long-term UWS and MCS after serious brain injury have increased significantly in recent decades [9]. However, the existing grading scale showed up some disadvantages in identifying the consciousness levels of DOC patients [10]. Accurate assessment strategies are urgently needed. In this circumstance, MRI with different sequences is imported as a novel technique for DOC patients, with a purpose of overcome the shortage of traditional sequences in evaluating the consciousness level. In our study, FA and MD were discovered as potential indicators of DOC patients’ assessment.

The reticular formations of the brainstem, thalamus, and subcortex are all related to consciousness in different degrees [11–13]. Therefore, this study selected these three regions as the ROIs to investigate the application value of DTI in imaging grading for DOC patients.

DTI can detect the diffusion direction of water molecules and the diffusion degree in each direction. This imaging technology is a special form of MR imaging, which was developed and established based on diffusion-weighted imaging (DWI). DTI has been widely used in multiple studies on neurological diseases, such as brain tumors, cerebral infarctions, and Alzheimer's disease. In particular, DTI can detect the damage in white matter fiber tracts caused by a variety of diseases [14].

The common indicators of DTI are FA, ADC (apparent diffusion coefficient), and MD [15]. FA refers to the ratio of the anisotropy of water molecules to the gross diffusion tensor, which ranges from 0 to 1. The closer the value is to 1, the higher degree of density of axon myelination, suggesting higher white matter integrity and less damage present in neurons and nerve fibers [16]. Yi et al [6] found that while computed tomography (CT) and MRI examinations for some patients with early diffuse axonal injury (DAI) revealed no hemorrhage or edema lesions, a DTI scan showed a decreased FA value at the damage site, reflecting the sensitivity of DTI to the changes in nerve fibers. In 2011, DTI began to be used in DOC research. Studies have found that the FA values in the thalamus of DOC patients were decreased to varying degrees, suggesting that DTI was specific in identifying the two states of UWS and MCS [17, 18]. We have now recognized the DTI's values in many brain pathologies, including DOC. An interesting case report on one 76-year-old man with UWS. He was examined with DTI reported an early FA reduction in 11 white matter regions that preceded macroscopic MRI and postmortem neuropathological findings. Some other researches focused on the similar ROIs, investigated diffusion alterations in the coma survivors of cardiac arrest. Abnormally dynamic FA values could be found after injury and predict unfavorable outcome with 94% sensitivity and 100% specificity.

Another study found that DTI could potentially distinguish UWS and MCS patients. Diffusion in MCS and UWS patients appeared to differ significantly in subcortical white matter and thalamic regions but appeared not to differ that much in the brainstem. Compared with the MCS group, the FA values of the UWS group were decreased, which may be due to increased permeability of the cell membranes at the injury sites of the patients. This increased permeability could lead to destruction of the integrity of the nerve fiber myelin so that the movement of water molecules was decreased in the axons and enhanced in the vertical direction. The change is less severe in MCS patients. Alternatively, the extent of the damage in the white matter fiber tracts might have improved in patients after recovering from UWS to MCS.

MD is another commonly used indicator in DTI, reflecting the diffusion capacity of water molecules. MD decreases in aging patients and therefore is a potential surrogate measurement for white matter maturation [19]. In this study, two groups of patients with different levels of DOC showed statistically significant differences in their ROIs. As an explanation for this difference, in comparison with the MCS group, the damage to the ROIs of the brain tissue of the UWS patients was more severe, and the patients were in deeper comas. This minor difference cannot be distinguished via conventional imaging examinations.

The DTI value of assessment were also found in some recent multi-centric studies in traumatic and anoxic patients regarding 1-year outcome. Furthermore, the combination of DTI and MRI spectroscopy has shown the potential ability to predict long-term outcome of DOC patients. Person correlation analysis also found that the FA values and the clinical CRS-R scores were positively correlated, especially in the thalamus, which may be due to the importance of the non-projection system in these regions for the arousal and consciousness state of the brain, which shows the closest relationship with the CRS-R score. The MD values and CRS-R scores in the ROIs showed a negative correlation; that is, the smaller the MD value was, the lower the severity of brain damage. Thus, to some extent, the changes in DTI indicators can reflect the consciousness level of DOC patients and whether the consciousness level improves.

In conclusion, using DTI technology, in DOC patients, the degrees of damage to the nerves and the white matter can be detected at a high level of sensitivity, and the recovery of the nerve fibers can be determined early [20]. By measuring each indicator, the extent of damage can be quantified. Therefore, as an important supplement technique and assessment tool, DTI technology can provide an objective and accurate evaluation of the state of consciousness for the patients to reduce the rates of misdiagnosis and delayed diagnosis with a certain clinical reference value and can add significance to further research. However, it should be noted that the number of patients in the MCS group in this study was relatively small. The correlations between the indicators and the state of consciousness and the CRS-R need to be further investigated using a larger sample size.