endovascular embolization has become a method of choice for the treatment of intracranial aneurysms in many centers . however , an important disadvantage of aneurysm coiling is the observed significant rate of recanalization that occurs on average in 20% of patients .
therefore , follow - up imaging of coiled aneurysms is recommended to prevent aneurysm recurrence and possible subsequent subarachnoid hemorrhage [ 57 ] .
the role of intra - arterial digital subtraction angiography ( dsa ) as a standard follow - up method for embolized aneurysms has been questioned   because of its invasiveness , need for hospitalization and relatively high cost . instead , magnetic resonance angiography ( mra ) has been proposed for this purpose as being less invasive and presenting very good accuracy in detecting residual flow in aneurysms [ 810 ] .
the question of whether time - of - flight mra ( tof - mra ) or contrast - enhanced mra ( ce - mra ) is a better method for aneurysm follow - up remains unresolved . despite a higher signal intensity and a higher signal - to - noise ratio of ce - mra , both techniques present similar specificity and sensitivity in detecting residual flow in aneurysms .
these drawbacks may be overcome by using time - resolved ce - mra , which enables imaging of cerebral vessels in several consecutive phases of contrast medium inflow .
this study was a prospective comparison of the diagnostic value of tof - mra and time - resolved ce - mra at follow - up of embolized intracranial aneurysms regarding the determination of aneurysm occlusion .
the study was approved by the university institutional review board and was performed in accordance with the declaration of helsinki .
the study was based on a population of patients that participated in a prospective single - center study comparing the diagnostic value of dsa and mra in the follow - up of ruptured intracranial aneurysms ( serafin z. et al .
patients treated for subarachnoid hemorrhage due to aneurysm rupture , who presented for the first follow - up imaging at 3 months after the procedure , were included in the study .
the exclusion criteria were : ( a ) age under 18 years ; ( b ) contraindications to mr imaging , including severe claustrophobia , ferromagnetic foreign bodies or electronic implants ; ( c ) the presence of neurosurgical clips ; and ( d ) estimated glomerular filtration rate ( egfr ) < 60 ml / min/1.73 m. embolizations were performed using platinum coils ( gdc detachable coils , boston scientific , natick , usa ; axium and nexus , ev3 corporate , plymouth , usa ; microplex , microvention , inc . , tustin , usa ) and hydrogel coils ( hydrocoil and hydrosoft , microvention , inc . , tustin , usa ) . in 8 patients with broad - neck aneurysms , intracranial stents ( neuroform3 , boston scientific , natick , usa )
were implanted prior to the coiling to achieve a better packing density and to prevent coil prolapse to the parent artery .
after the embolization , the baseline status of the aneurysm was documented by dsa , including both 2-dimensional ( 2d ) and 3-dimensional ( 3d ) acquisitions .
follow - up dsa was performed using a monoplane angiographic unit ( axiom artis dta , siemens medical systems , erlangen , germany ) by means of transfemoral catheterization .
the examination included 4-vessel 2-d dsa and 3-d dsa of an artery with an embolized aneurysm . the contrast agent ( iopromide , ultravist 300 mg - i / ml , bayer schering pharma ag , berlin , germany ) was administered with a power injector through a 5-f catheter .
images were analyzed on a dedicated workstation ( syngo xvp va72b , siemens ag , berlin , germany ) using inspace 3-d software .
mr angiography was performed with a 1.5 t signa hdx unit , using an 8-channel hd brain coil ( ge medical systems , waukesha , wi , usa ) within 24 hours after dsa .
the examination consisted of 2 sequences : tof - mra and time - resolved imaging of contrast kinetics ( tricks ) .
tof - mra was performed with a 3-d tof asset multislab technique in an axial plane ( te 2.7 ms , tr 30 ms , flip angle 20 , bandwidth 31.25 khz , section thickness 1.2 mm , matrix 320224 ) .
tricks acquisition consisted of 6 3-d phases in a coronal plane ( te 1.5 ms , tr 3.5 ms , flip angle 25 , bandwidth 83.33 khz , section thickness 2.2 mm , matrix 288192 , temporal resolution 3 s ) .
contrast medium ( gadobenate dimeglumine , gd - bopta , multihance , 0.5 mmol / ml , bracco imaging deutschland gmbh , konstanz , germany ) was administered by a power injection in a dose of 0.1 mmol / kg b.w . at 2
the final analysis was based on a phase that presented optimal delineation of arteries without significant contamination by venous enhancement ( figure 1 ) .
angiograms were evaluated with advantage workstation 4.4 and volume share 8.4.3 software ( ge medical systems , waukesha , wi , usa ) .
the analysis included non - reconstructed images , as well as mpr , mip and vr reconstructions .
the examinations were independently assessed by 2 interventional neuroradiologists ( z.s , p.s . ) with 10 years of experience in the field .
the observers evaluated blinded data , and were unaware of the other imaging results of the patient .
images were evaluated for the detection of residual flow in the aneurysm , quantification of the flow ( ie , classification of the degree of aneurysm occlusion ( class 13 according to roy et al . ) , and possibility of retreatment .
the reference result was established retrospectively when results of index tests were set in all the study participants .
the reference test was dsa , which constituted a simultaneous analysis of 2-d dsa images , 3-d dsa vr reconstructions , and source rotational dsa images .
the quality of visualization was graded using a subjective semiquantitative scoring method that was proposed by gibbs et al . .
the tof - mra and tricks examinations were evaluated for overall quality of parent artery delineation , distal vessel identification , vascular signal intensity , and motion artifacts .
each examination was given a score on a 5-point scale : 5 signified excellent quality ; 4 , more than adequate quality for diagnosis ; 3 , adequate quality for diagnosis ; 2 , less than adequate quality for diagnosis ; and 1 , non - diagnostic .
the wilcoxon signed - rank test was used to determine any statistically significant difference in image quality .
the quantitative assessment of image quality was based on calculation of contrast - to - noise ratio ( cnr ) and signal - to - noise ratio ( snr ) .
arterial signal intensity ( sia ) of the mid - segments of basilar arteries was measured on non - reconstructed images in regions of interest ( roi ) of 23 mm , depending of the artery diameter .
background signal intensity ( sib ) was measured in the brain stem in rois of 20 mm on average .
the image noise was measured as the sd of air signal intensity ( sdn ) outside the skull in rois of 20 mm on average .
snr and cnr for each examination were calculated as follows : snr = sia / sdn ; cnr=(siasib)/sdn .
test characteristics of tof - mra and tricks vs. dsa as a reference were calculated with corresponding 95% ci and expressed the ability of index tests to properly detect residual flow in the aneurysm .
the test characteristics included sensitivity , specificity , positive predictive value ( ppv ) , negative predictive value ( npv ) , positive likelihood ratio ( lr+ ) , negative likelihood ratio ( lr ) , and diagnostic accuracy .
the areas under the receiver operating characteristic curves ( aucs ) with their 95% cis were also calculated .
significance of the auc values and significance of differences between them was tested with the z - test .
the ability of tof - mra and tricks to properly classify the degree of aneurysm occlusion ( class 13 ) was assessed with concordance correlation coefficient ( ccc ) with its 95% ci and weighted cohen s kappa (  ) .
intraobserver agreement and interobserver agreement were measured with cohen s  with its 95% ci . a p - value of < 0.05 was considered significant .
statistical analyses were performed using medcalc 11.6.0 ( medcalc software , mariakerke , belgium ) and statistica 9 ( statsoft inc . , tulsa , usa ) .
the study was approved by the university institutional review board and was performed in accordance with the declaration of helsinki .
the study was based on a population of patients that participated in a prospective single - center study comparing the diagnostic value of dsa and mra in the follow - up of ruptured intracranial aneurysms ( serafin z. et al .
patients treated for subarachnoid hemorrhage due to aneurysm rupture , who presented for the first follow - up imaging at 3 months after the procedure , were included in the study .
the exclusion criteria were : ( a ) age under 18 years ; ( b ) contraindications to mr imaging , including severe claustrophobia , ferromagnetic foreign bodies or electronic implants ; ( c ) the presence of neurosurgical clips ; and ( d ) estimated glomerular filtration rate ( egfr ) < 60 ml / min/1.73 m. embolizations were performed using platinum coils ( gdc detachable coils , boston scientific , natick , usa ; axium and nexus , ev3 corporate , plymouth , usa ; microplex , microvention , inc . , tustin , usa ) and hydrogel coils ( hydrocoil and hydrosoft , microvention , inc . , tustin , usa ) . in 8 patients with broad - neck aneurysms , intracranial stents ( neuroform3 , boston scientific , natick , usa )
were implanted prior to the coiling to achieve a better packing density and to prevent coil prolapse to the parent artery .
after the embolization , the baseline status of the aneurysm was documented by dsa , including both 2-dimensional ( 2d ) and 3-dimensional ( 3d ) acquisitions .
follow - up dsa was performed using a monoplane angiographic unit ( axiom artis dta , siemens medical systems , erlangen , germany ) by means of transfemoral catheterization .
the examination included 4-vessel 2-d dsa and 3-d dsa of an artery with an embolized aneurysm . the contrast agent ( iopromide , ultravist 300 mg - i / ml , bayer schering pharma ag , berlin , germany ) was administered with a power injector through a 5-f catheter .
images were analyzed on a dedicated workstation ( syngo xvp va72b , siemens ag , berlin , germany ) using inspace 3-d software .
mr angiography was performed with a 1.5 t signa hdx unit , using an 8-channel hd brain coil ( ge medical systems , waukesha , wi , usa ) within 24 hours after dsa . the examination consisted of 2 sequences : tof - mra and time - resolved imaging of contrast kinetics ( tricks ) .
tof - mra was performed with a 3-d tof asset multislab technique in an axial plane ( te 2.7 ms , tr 30 ms , flip angle 20 , bandwidth 31.25 khz , section thickness 1.2 mm , matrix 320224 ) .
tricks acquisition consisted of 6 3-d phases in a coronal plane ( te 1.5 ms , tr 3.5 ms , flip angle 25 , bandwidth 83.33 khz , section thickness 2.2 mm , matrix 288192 , temporal resolution 3 s ) .
contrast medium ( gadobenate dimeglumine , gd - bopta , multihance , 0.5 mmol / ml , bracco imaging deutschland gmbh , konstanz , germany ) was administered by a power injection in a dose of 0.1 mmol / kg b.w . at 2
the final analysis was based on a phase that presented optimal delineation of arteries without significant contamination by venous enhancement ( figure 1 ) .
angiograms were evaluated with advantage workstation 4.4 and volume share 8.4.3 software ( ge medical systems , waukesha , wi , usa ) .
the analysis included non - reconstructed images , as well as mpr , mip and vr reconstructions .
the examinations were independently assessed by 2 interventional neuroradiologists ( z.s , p.s . ) with 10 years of experience in the field .
the observers evaluated blinded data , and were unaware of the other imaging results of the patient .
images were evaluated for the detection of residual flow in the aneurysm , quantification of the flow ( ie , classification of the degree of aneurysm occlusion ( class 13 according to roy et al . ) , and possibility of retreatment .
the reference result was established retrospectively when results of index tests were set in all the study participants .
the reference test was dsa , which constituted a simultaneous analysis of 2-d dsa images , 3-d dsa vr reconstructions , and source rotational dsa images .
parametric variables were expressed as mean values  standard deviation ( sd ) . the quality of visualization was graded using a subjective semiquantitative scoring method that was proposed by gibbs et al . .
the tof - mra and tricks examinations were evaluated for overall quality of parent artery delineation , distal vessel identification , vascular signal intensity , and motion artifacts .
each examination was given a score on a 5-point scale : 5 signified excellent quality ; 4 , more than adequate quality for diagnosis ; 3 , adequate quality for diagnosis ; 2 , less than adequate quality for diagnosis ; and 1 , non - diagnostic .
the wilcoxon signed - rank test was used to determine any statistically significant difference in image quality .
the quantitative assessment of image quality was based on calculation of contrast - to - noise ratio ( cnr ) and signal - to - noise ratio ( snr ) .
arterial signal intensity ( sia ) of the mid - segments of basilar arteries was measured on non - reconstructed images in regions of interest ( roi ) of 23 mm , depending of the artery diameter .
background signal intensity ( sib ) was measured in the brain stem in rois of 20 mm on average .
the image noise was measured as the sd of air signal intensity ( sdn ) outside the skull in rois of 20 mm on average .
snr and cnr for each examination were calculated as follows : snr = sia / sdn ; cnr=(siasib)/sdn .
test characteristics of tof - mra and tricks vs. dsa as a reference were calculated with corresponding 95% ci and expressed the ability of index tests to properly detect residual flow in the aneurysm .
the test characteristics included sensitivity , specificity , positive predictive value ( ppv ) , negative predictive value ( npv ) , positive likelihood ratio ( lr+ ) , negative likelihood ratio ( lr ) , and diagnostic accuracy .
the areas under the receiver operating characteristic curves ( aucs ) with their 95% cis were also calculated .
significance of the auc values and significance of differences between them was tested with the z - test .
the ability of tof - mra and tricks to properly classify the degree of aneurysm occlusion ( class 13 ) was assessed with concordance correlation coefficient ( ccc ) with its 95% ci and weighted cohen s kappa (  ) .
intraobserver agreement and interobserver agreement were measured with cohen s  with its 95% ci . a p - value of < 0.05 was considered significant .
statistical analyses were performed using medcalc 11.6.0 ( medcalc software , mariakerke , belgium ) and statistica 9 ( statsoft inc . ,
between november 2009 and march 2011 , 74 patients with 74 aneurysms were included in this prospective study .
thus , 72 patients ( mean age 51.512.4 years ) , including 24 men and 48 women , were finally analyzed ( table 1 ) .
there were no adverse reactions to contrast media during follow - up and there were no adverse events specifically related to dsa .
the reference test revealed residual flow in 26 aneurysms ( 36.1% ) ( figure 2 ) .
the flow area was classified as class 2 ( residual neck ) in 8 cases ( 11.1% ) and as class 3 ( residual aneurysm ) in 18 cases ( 25.0% ) .
the mean quality score for tof - mra and tricks images was 4.080.64 and 3.880.67 , respectively ( p<0.03 ) .
on the other hand , both snr and cnr of tricks images were significantly higher than those of tof - mra  140.545.8 and 84.628.8 compared to 200.2146.3 and 182.0124.3 , respectively ( p<0.002 ) .
the tof - mra correctly diagnosed complete occlusion in 42 patients and residual flow in 22 patients , while 4 diagnoses were false - positive and 4 were false - negative ( figure 3 ) .
however , in all cases treated with stent - assisted coiling , the signal intensity was slightly decreased within the stent lumen .
the decrease of the signal intensity was less pronounced on tricks images than on tof - mra images and did not influence the evaluation of aneurysms .
detection of the residual flow in tricks was true - positive in 23 cases , false - positive in 4 cases , false - negative in 3 cases , and true - negative in 42 patients .
the quantification of the occlusion status of an aneurysm was more accurate with tricks ( =0.83 ; ccc=0.86 ; 95% ci : 0.790.91 ) than with tof - mra ( =0.76 ; ccc=0.80 ; 95% ci : 0.700.87 ) , while auc values were not significantly different between the 2 methods ( 0.90 , 95% ci : 0.810.96 and 0.88 , 95% ci : 0.780.94 , respectively ) .
both tof - mra and tricks presented good or very good reproducibility for detecting the residual flow .
intraobserver agreement was 0.86 ( 95% ci : 0.740.98 ) for tof - mra and 0.89 ( 95% ci : 0.780.99 ) for tricks .
interobserver agreement was 0.74 ( 95% ci : 0.590.90 ) for tof - mra and 0.80 ( 95% ci : 0.670.94 ) for tricks .
despite the fact that for many years dsa has been a standard diagnostic method for follow - up of embolized aneurysms , mr examination has become an accepted comprehensive alternative to invasive imaging , especially in outpatient practice .
however , the most advantageous mra technique for follow - up remains the subject of debate .
a meta - analysis by kwee and kwee , which included 16 primary studies , revealed no statistically significant differences in pooled sensitivity and specificity between tof - mra and ce - mra in detecting residual flow in the aneurysm .
similarly , in the largest recently published prospective study with 311 patients by schaafsma et al . , the areas under the receiver operating characteristic curves of the 2 methods were not statistically different .
on the other hand , kaufmann et al recommend performing both ce - mra and tof - mra to increase the accuracy of the examination .
the main disadvantage of tof - mra is its low sensitivity to slow and turbulent blood flow because of intravoxel dephasing and spin saturation .
therefore , the slow residual flow within the coil mesh and tortuous remnants may not be detected due to signal loss , resulting in false - negative results .
ce - mra better depicts areas of slow and turbulent flow and results in fewer flow - related artifacts . on the other hand , the use of contrast medium may cause an enhancement of the vasa vasorum and an organized thrombus , which is likely to produce false - positive results . finally ,
if a single long ce - mra acquisition is performed without well - timed contrast triggering , venous enhancement can significantly reduce image quality . in both tof - mra and ce - mra ,
a subacute thrombus , which has a high signal on t1-weighted images , may simulate the residual flow . theoretically , the use of the 4-dimensional tricks technique may help to overcome some shortcomings of the conventional static first - pass ce - mra in the follow - up of embolized aneurysms .
since tricks offers dynamic images of blood flow , it may be more sensitive to areas of residual filling within the coil mesh .
moreover , image contamination by venous enhancement may be avoided by selecting a proper inflow phase through comparison of consecutive phases .
similarly , enhancement of the vasa vasorum and organized thrombus should be more clearly distinguished from aneurysm remnants . in our study tricks
we noted a decrease of signal intensity in stented segments of parent arteries , which was related to susceptibility artifacts .
similar artifacts have already been observed by several authors   and the intensity of such artifacts seems to depend on the type of stent used for embolization .
the application of time - resolved contrast - enhanced mra has been reported in the investigation of extracerebral aneurysms , arteriovenous malformations and dural arteriovenous fistulas , and as a cerebral venography technique [ 2023 ] .
it was also tested as a method for imaging guidance in experimental aneurysm embolizations under mr control . to our knowledge
, the diagnostic value of tricks and tof - mra in the follow - up of embolized intracranial aneurysms has not been previously compared .
we found that although tricks images had significantly higher snr and cnr than tof - mra , which was a result of contrast medium administration , their quality scored lower .
more importantly , tricks was only slightly more accurate in detecting the residual flow and in quantifying the status of aneurysm occlusion with auc values not statistically different .
the received values of sensitivity and specificity of tricks ( 88.5% , 95% ci : 69.897.4% and 91.3% , 95% ci : 79.297.5% ) are comparable to those of the conventional static ce - mra reported in the literature [ 812 ] .
firstly , the sample size appears to be insufficient to demonstrate the significance of the difference between the diagnostic value of tricks and tof - mra .
it still may be hypothesized that the demonstrated small difference in auc might appear significant in a larger population .
secondly , there was a possibility to increase spatial resolution of tricks examinations ; however , this would result in a decrease of temporal resolution .
since both parameters were considered important to our study , the applied settings present , in our opinion , a reasonable compromise .
our results indicate that the use of time - resolved imaging of contrast kinetics does not improve the diagnostic value of mra in the follow - up of embolized intracranial aneurysms .
because tof - mra has a similar diagnostic performance and does not expose patients to contrast media , it should be considered a first - line alternative to dsa in routine outpatient follow - up .
 summarybackgroundthe use of contrast media and the time - resolved imaging of contrast kinetics ( tricks ) technique have some theoretical advantages over time - of - flight magnetic resonance angiography ( tof - mra ) in the follow - up of intracranial aneurysms after endovascular treatment . 
 we prospectively compared the diagnostic performance of tricks and tof - mra with digital subtracted angiography ( dsa ) in the assessment of occlusion of embolized aneurysms.material/methodsseventy-two consecutive patients with 72 aneurysms were examined 3 months after embolization . 
 test characteristics of tof - mra and tricks were calculated for the detection of residual flow . 
 the results of quantification of flow were compared with weighted kappa . 
 intraobserver and interobserver reproducibility was determined.resultsthe sensitivity of tof - mra was 85% ( 95% ci , 6596% ) and of tricks , 89% ( 95% ci , 7097% ) . 
 the specificity of both methods was 91% ( 95% ci , 7998% ) . 
 the accuracy of the flow quantification ranged from 0.76 ( tof - mra ) to 0.83 ( tricks ) . 
 there was no significant difference between the methods in the area under the roc curve regarding both the detection and the quantification of flow . 
 intraobserver reproducibility was very good with both techniques ( kappa , 0.860.89 ) . 
 the interobserver reproducibility was moderate for tof - mra and very good for tricks ( kappa , 0.740.80).conclusionsin this study , tof - mra and tricks presented similar diagnostic performance ; therefore , the use of time - resolved contrast - enhanced mra is not justified in the follow - up of embolized aneurysms . 
Background
Material and Methods
Population
Follow-up technique
Image analysis
Calculations and statistical analysis
Results
Discussion
Conclusions