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impaired consciousness is caused by injury of the ascending reticular activating system ( aras ) .
the aras is a complicated neural structure which can not be definitely discriminated from adjacent neural structures on conventional brain mri .
diffusion tensor tractography ( dtt ) , which is derived from diffusion tensor imaging ( dti ) , enabled evaluation of the aras by 3-dimensional reconstruction in the human brain .
a few studies using dtt have reported on recovery of consciousness and an injured aras in chronic patients ; however , little is known about recovery at an early stage of brain injury . in this study
, we report on a patient who survived cardiac arrest and showed recovery of consciousness and an injured aras at the early stage of hypoxic - ischemic brain injury ( hi - bi ) for 3 weeks , which was demonstrated by dtt .
a 52-year - old male patient suffered cardiac arrest caused by acute coronary syndrome and was resuscitated immediately by a layman and paramedics for 25 minutes .
he was then transferred immediately to the emergency room of a local medical center . at 2 weeks after onset
, he was transferred to the rehabilitation department of a university hospital to undergo rehabilitation .
his consciousness was impaired , with a glasgow coma scale ( gcs ) score of 8 ( eye opening : 2 , best verbal response : 2 , and best motor response : 4 ) and coma recovery scale - revised ( grs - r ) score of 8 ( auditory function : 1 , visual function : 1 , motor function : 3 , verbal function : 2 , communication : 1 , and arousal : 0 ) .
no abnormal lesion was observed on brain mri taken at 2 weeks after onset ( fig .
he underwent comprehensive rehabilitative therapy , including drugs for recovery of consciousness ( modafinil , levodopa , ropinirole , amantadine , zolpidem , and donepezil ) , physical therapy , and occupational therapy .
he recovered well and rapidly so that his consciousness had recovered to full scores in terms of gcs:15 and grs - r:23 at 5 weeks after onset .
therefore , he was able to walk independently and was evaluated with a score of 9 on the mini - mental state examination ( full score : 30 ) .
the patient 's wife provided signed , informed consent , and the study protocol was approved by the institutional review board yeungnam university hospital .
( a ) brain mr images taken at 2 and 5 weeks after onset show no abnormal lesion .
( b ) results of diffusion tensor tractography ( dtt ) of the patient . on 5-week dtt ,
the left lower dorsal ( green arrow ) and right lower ventral ( blue arrow ) ascending reticular activating system had become thicker compared with 2-week dtt .
increased neural connectivity of the thalamic intralaminar nucleus to the basal forebrain and prefrontal cortex ( red arrows ) was observed in both hemispheres on 5-week dtt compared with 2-week dtt . a normal control subject ( 53-year - old male ) .
dti data were acquired 2 times ( 2 and 5 weeks after onset ) using a 6-channel head coil on a 1.5 t philips gyroscan intera ( philips , best , netherlands ) .
imaging parameters were as follows : echo - planar imaging factor49 ; repetition time10,726 ms ; reconstructed matrix192    192 ; b1000  s / mm ; echo time76 ms ; number of excitations1 ; and a slice thickness of 2.5  mm with no gap ( acquired isotropic voxel size 1.3    1.3    2.5  mm ) .
the oxford centre for functional magnetic resonance imaging of the brain ( fmrib ) software library was used for the analysis of dti data .
fmrib diffusion software was used for fiber tracking with the following options ( step lengths : 0.5  mm , streamline samples : 5000 , curvature thresholds : 0.2 ) .
three portions of the aras were reconstructed by selection of fibers passing through the following regions of interest ( rois ) : the dorsal lower aras ; the seed roi : the pontine reticular formation ( rf ) , and the target roi : the thalamic intralaminar nucleus ( iln ) .
the ventral lower aras ; the seed roi : the pontine rf , and the target roi : the hypothalamus , and the upper aras ; the seed roi : the neural connectivity of the iln to the cerebral cortex was analyzed .
out of 5000 samples generated from the seed voxel , results for contact were visualized at a minimum threshold for the lower ( dorsal , ventral ) aras of 2 and for neural connectivity of the iln of 15 streamlined through each voxel for analysis .
dtt parameters ( fractional anisotropy [ fa ] and tract volume [ tv ] ) were measured for the lower dorsal aras , lower ventral aras and upper aras of the patient , and 10 age- and sex - matched normal control subjects ( male : 10 , mean age : 54.1 years ) .
dtt parameters showing a deviation of > 2 standard deviations from normal control values were defined as abnormal .
a summary of the values of fa and tv of the lower dorsal aras , lower ventral aras , and upper aras of the patient and normal control subjects is shown in table 1 .
on 2-week dtt , tvs of the left lower dorsal aras , right lower ventral aras , and both upper aras were > 2 standard deviations below those of normal control subjects , respectively , whereas on 5-week dtt , these values had increased to within 2 standard deviations of those of normal control subjects . regarding configuration of dtt ,
the left lower dorsal and right lower ventral aras had become thicker on 5-week dtt compared with 2-week dtt ( fig .
regarding the change of neural connectivity of the thalamic iln , increased neural connectivity to the basal forebrain and prefrontal cortex was observed in both hemispheres on 5-week dtt compared with 2-week dtt .
comparisons of diffusion tensor imaging parameters for the lower dorsal ascending reticular activating system , lower ventral and upper portion of the ascending reticular activating system between the patient and control subjects .
dti data were acquired 2 times ( 2 and 5 weeks after onset ) using a 6-channel head coil on a 1.5 t philips gyroscan intera ( philips , best , netherlands ) .
imaging parameters were as follows : echo - planar imaging factor49 ; repetition time10,726 ms ; reconstructed matrix192    192 ; b1000  s / mm ; echo time76 ms ; number of excitations1 ; and a slice thickness of 2.5  mm with no gap ( acquired isotropic voxel size 1.3    1.3    2.5  mm ) .
the oxford centre for functional magnetic resonance imaging of the brain ( fmrib ) software library was used for the analysis of dti data .
fmrib diffusion software was used for fiber tracking with the following options ( step lengths : 0.5  mm , streamline samples : 5000 , curvature thresholds : 0.2 ) .
three portions of the aras were reconstructed by selection of fibers passing through the following regions of interest ( rois ) : the dorsal lower aras ; the seed roi : the pontine reticular formation ( rf ) , and the target roi : the thalamic intralaminar nucleus ( iln ) . the ventral lower aras ; the seed roi : the pontine rf , and the target roi : the hypothalamus , and the upper aras ; the seed roi : the neural connectivity of the iln to the cerebral cortex was analyzed .
out of 5000 samples generated from the seed voxel , results for contact were visualized at a minimum threshold for the lower ( dorsal , ventral ) aras of 2 and for neural connectivity of the iln of 15 streamlined through each voxel for analysis .
dtt parameters ( fractional anisotropy [ fa ] and tract volume [ tv ] ) were measured for the lower dorsal aras , lower ventral aras and upper aras of the patient , and 10 age- and sex - matched normal control subjects ( male : 10 , mean age : 54.1 years ) .
dtt parameters showing a deviation of > 2 standard deviations from normal control values were defined as abnormal .
a summary of the values of fa and tv of the lower dorsal aras , lower ventral aras , and upper aras of the patient and normal control subjects is shown in table 1 .
on 2-week dtt , tvs of the left lower dorsal aras , right lower ventral aras , and both upper aras were > 2 standard deviations below those of normal control subjects , respectively , whereas on 5-week dtt , these values had increased to within 2 standard deviations of those of normal control subjects . regarding configuration of dtt ,
the left lower dorsal and right lower ventral aras had become thicker on 5-week dtt compared with 2-week dtt ( fig .
1b ) . regarding the change of neural connectivity of the thalamic iln , increased neural connectivity to the basal forebrain and prefrontal cortex was observed in both hemispheres on 5-week dtt compared with 2-week dtt .
comparisons of diffusion tensor imaging parameters for the lower dorsal ascending reticular activating system , lower ventral and upper portion of the ascending reticular activating system between the patient and control subjects .
in the present study , using dtt , change of the aras was evaluated in a patient who survived cardiac arrest whose consciousness showed rapid and good recovery for 3 weeks at the early stage of hi - bi .
the patient 's impaired consciousness showed full recovery during 3 week 's rehabilitation from 2 weeks ( gcs : 8) to 5 weeks ( gcs : 15 ) after onset .
the changes of the aras were as follows : ( 1 ) the narrowed left lower dorsal ( tv : 202  332 ) and right ventral aras ( tv : 14  170 ) observed on 2-week dtt had become thicker on 5-week dtt and ( 2 ) the decreased neural connectivity to both basal forebrain and prefrontal cortex ( tv : right6206  8736 and left6113  8331 ) observed on 2-week dtt had increased on 5-week dtt .
the fa value indicates the white matter organization and degree of directionality , and the tv indicates total number of voxels within a neural tract .
therefore , the increment of tv value without change of fa value of the left lower dorsal aras , right lower ventral aras , and both upper aras observed on 5-week dtt appeared to indicate recovery of the injured aras .
the narrowing of the lower aras and decreased neural connectivity of the upper aras indicated neural injury of the aras by hi - bi .
therefore , thickening of the narrowed lower aras and increased connectivity to both basal forebrain and prefrontal cortex , which are important areas of the brain for consciousness , appears to be in agreement with the improved consciousness observed in this patient .
in addition , the changes of the injured aras were comparable with those reported in previous studies on the recovery of consciousness and an injured aras . in conclusion , recovery of an injured aras was demonstrated in a patient who survived cardiac arrest who showed rapid and good recovery of consciousness for 3 weeks at the early stage of hi - bi .
a few studies have reported on the recovery of an injured aras in patients with brain injury , using follow up dtt . in 2015 , jang et al reported on a patient with traumatic brain injury who showed recovery of an injured lower dorsal aras , by demonstrating changes on dtt at 4-and 40 months after onset .
subsequently , jang and lee reported on the recovery of an injured aras in terms of the configuration of the lower dorsal aras , and the neural connectivity of the upper aras in a patient with hypoxic ischemic brain injury from 7 months to 45 months after onset .
jang et al recently reported on a patient with traumatic brain injury for 2 months from 10 months to 12 months after onset following a shunt operation for hydrocephalus .
therefore , this is the first study to demonstrate recovery of the aras at the early stage of brain injury in a patient who survived cardiac arrest .
however , the limitation of dtt should be considered : dtt may be underestimated due to regions of fiber complexity and crossing .
abstractwe report on a patient who survived cardiac arrest and showed recovery of consciousness and an injured aras at the early stage of hypoxic - ischemic brain injury ( hi- bi ) for 3 weeks , which was demonstrated by diffusion tensor tractography ( dtt).a 52-year - old male patient who had suffered cardiac arrest caused by acute coronary syndrome was resuscitated immediately by a layman and paramedics for 25 minutes . 
 he was then transferred immediately to the emergency room of a local medical center . when starting rehabilitation at 2 weeks after onset , his consciousness was impaired , with a glasgow coma scale ( gcs ) score of 8 and coma recovery scale - revised ( grs - r ) score of 8 . 
 he underwent comprehensive rehabilitative therapy , including drugs for recovery of consciousness . 
 he recovered well and rapidly so that his consciousness had recovered to full scores in terms of gcs:15 and grs - r:23 at 5 weeks after onset.the left lower dorsal and right lower ventral aras had become thicker on 5-week dtt compared with 2-week dtt ( fig . 
 1b ) . 
 regarding the change of neural connectivity of the thalamic iln , increased neural connectivity to the basal forebrain and prefrontal cortex was observed in both hemispheres on 5-week dtt compared with 2-week dtt.recovery of an injured aras was demonstrated in a patient who survived cardiac arrest and his consciousness showed rapid and good recovery for 3 weeks at the early stage of hi - bi .