| Object i ve To establish an animal model of diffuse brain injury, and observe the spatiotemporal features of diffuse tensor imaging (DTI) and susceptibility-weighted imaging (SWI) post-trauma, and furtherly investigate the correlation between imaging data and animal’s pathological and neurological alterations. To observe the spatiotemporal features of MR imaging (DTI&SWI) in traumatic brain injury (TBI) patient at three post-trauma time points, i.e., acute phase, subacute phase, and1-3months following trauma, and evaluate the correlation between imaging data and clinical scores, and finally explore the value of these two advanced MR techniques specific to different post-trauma phase in determining the pathophysiological condition, monitoring the disease progression, and predicting the prognosis of TBI.Materials and methods1. Fifty-one New Zealand rabbits were randomly divided into control group (n=3) and injured group (n=48). An instant rotating device were employed and two different rotation angle were prescribed to induce the mild (n=24) and severe (n=24) diffuse axonal injury (DAI) respectively. Each injured group was subdivided into8subgroups (n=3) corresponding to eight observation time points, which were1h,6h,12h,24h,48h,72h,1w, and2w post injury, respectively. A pre-injury MRI examination including conventional MRI, DTI, and SWI was performed. Behavioral alterations were recorded and neurological severity scale (NSS) was executed post injury. The same MRI protocol was performed at specific time points following injury. Animals in each subgroup were sacrificed at specific time points and their brains were removed. HE staining and B-amyloid precursor protein (β-APP) immunohistochemical staining were employed for the microscopic observation. FA, ADC of subcortical white matter, corpus callosum, and brainstem, as well as blood phase value of specified veins (including internal cerebral vein, ventromedial vein, ventrolateral vein, dorsal sagittal sinus, dorsal cerebellar vein, median dorsal vein of brainstem) on the pre-and post-injury MRI images were measured. After comparing the pre-and post-injury phase images, we also recorded the incidence of "abnormal vessels sign" in the mild and severe injured group. The number of positive axons of per5×400high power fields in the subcortical white matter, corpus callosum, and brainstem were counted at each time point. The DTI metrics and blood phase values were compared between mild and severe injured groups. The temporal changes of the MRI data were observed and analyzed. The MRI measurements at different time points were correlated with NSS scores. The incidences of the "abnormal vessels sign", as well as the "remission type" and "progressive type" of "abnormal vessels sign" in the mild and severe injured groups were compared.2. Fifty-nine cases of TBI patients with a total89person-exams and60cases of matched healthy controls were performed with conventional MRI, DTI, and SWI exams. GCS scores within24h post-trauma and GOS scores at6months post-trauma were recorded. The imaging data of TBI patients were collected in three phases, including acute phase, subacute phase, and1-3months post-trauma. The TBI patients were divided into mild TBI group (GCS=13,35cases) and moderate-severe TBI group (GCS=12,24cases). According to the patients’GOS scores, the TBI patients were divided a good-outcome group (GOS4-5,44cases) and a poor-outcome group (GOS1-3,15cases).FA, ADC in the white matter, corpus callosum, internal capsule, cerebral peduncle, pons, and medulla, as well as blood phase value of specified veins (including internal cerebral vein, basal vein, superficial middle cerebral vein, superior sagittal sinus, cerebellar vein, median anterior vein of brainstem), of controls and TBI patients in different phases were measured. After comparing the phase images of controls and TBI patients, we recorded the incidence of "abnormal vessels sign" in the two TBI groups and the incidences of "abnormal vessels sign" of mild and moderate-severe TBI groups were compared. The data between controls and TBI patients, as well as between two TBI groups, were compared. The temporal changes of the MRI data were observed and analyzed. The measurements of different time points were correlated with the GCS scores respectively. The differences of MRI data between two outcome groups were also analyzed.Results1. Behavioral abnormalities were observed in DAI rabbits following injury. The number of B-APP positive axons in each predilection site peaked in24-48h post-injury. The numbers of severe injured group is higher than that of the mild injured group.2. Highly significant reductions in FA of DAI rabbits were noted at all time points within2w post-injury. The reduction in the severe injured group is much more obvious than that in the mild group. The negative correlations were revealed between FA of all time points with NSS scores. The FA between12h-72h post-injury negatively correlated with numbers of β-APP positive axons. ADC was significantly reduced within1w post-injury and went up from2w post-injury. Its correlations with NSS scores and numbers of β-APP positive axons were not as significant as FA.3. Blood phase values of specified veins of DAI rabbits were significantly reduced following injury. The values of severe injured group were significantly lower than those of mid injured group. Compared with those of the mild group, the blood phase valued of the severe group exhibited a trend of steady decline and delayed improvement. The phase values at the acute time points were statistically correlated with NSS scores, especially for the supratentorial superficial veins.4. The incidence of "abnormal vessels sign" of the severe injured rabbits was marked higher than that of the mild injured ones, and the incidence of "progressive type" of the severe group was also higher than that of mild injured group.5. FA of the majority of the observation sites were significantly reduced in the three post-injury phases of TBI patients, with exception of FA of corpus callosum and internal capsule in the mild group. FA significantly positively correlated with GCS, scores and its difference between two outcome groups was also significant. Even1-3months post-trauma, FA of the corpus callosum still exhibited the significance. ADC presented a complicated change post-trauma, and its correlations with GCS, GOS scores were not as significantly as FA.6. The blood phase values of mild TBI group presented a trend of descending in the acute phase, and climbing back after that. The decrease in the acute phase of the moderate-severe TBI group is more evident than that of the mild group. The blood phase values of the acute, subacute phases had a positive correlation with GCS scores and had a significant difference between two outcome groups, with a better performance of supratentorial superficial veins.7. The incidence of "abnormal vessels sign" in the moderate-severe TBI patients was significantly higher than that of the mild TBI patients.Conclusion1. The instant rotating device utilized in this study is simple, feasible, reproducible, which can be employed in the modeling of small DAI animals.2. FA indicates the underlying integrity of axons. The decreased FA correlates well with the injury severity of DAI animals, the severity and prognosis of TBI patients. The FA of corpus callosum and internal capsule in the acute phase exceptionally increases in the mild TBI patients, which suggests the presentence of cytoxic edema. Even in the1-3months post-trauma, the microscopic injury of axons still can be revealed by DTI.3. ADC presents a biphasic trend with time following trauma. Its correlations with the injury severity and prognosis are not as sensitive and accurate as FA. Changed ADC in association with FA changes could differentiate cytotoxic edema from vasogenic edema.4. Blood phase values available by SWI has the potential to be a biomarker of oxygen saturation and furtherly reflect the alterations of oxygen metabolism post-trauma.5. Reduction of blood phase values in the acute phase is noted in both DAI rabbits and TBI patients, which gradually rises in the subacute phase and hereafter. The reduction of blood phase values indicates the decrease of oxygen saturation and insufficient oxygenation of tissue.6. The "abnormal vessels sign" presented in the phase image of SWI suggests the diffuse brain injury and oxygen metabolisem abnormalities. Two types of "abnormal vessels sign" also can be observed in acute phase images of DAI rabbits.7. DTI and SWI depict different pathophysiological alterations following trauma. The employment of these two advanced MR techniques in combination or seperately can aid in the diagnosis, therapy, and prognosis prediction of TBI. |
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