The most significant finding of this study is that 4D-TRAK MRA is able to provide nearly all valid diagnoses of AVM and dAVF. Furthermore, our study also shows that 4D-TRAK MRA is superior to 3D TOF MRA in diagnostic accuracy and venous drainage assessment. Regarding interobserver agreement, 4D-TRAK MRA showed excellent agreement in terms of diagnostic accuracy and venous drainage, as well as moderate agreement in arterial feeder identification. 3D TOF MRA presented good agreement in diagnostic accuracy and artery feeder assessment and moderate agreement in venous drainage. In short, compared with 3D TOF MRA, 4D-TRAK MRA was shown to be more reliable in diagnosing cerebral AVM and dAVF.
Our study shows that almost all vascular lesions and venous drainage patterns can be correctly evaluated by 4D-TRAK MRA, which is here shown to be superior to 3D TOF MRA (
Tables 3 and
4). For the primary diagnosis of cerebral AVM and dAVF, or follow-up, the detection of early venous drainage is very important (
23,
30). 4D-TRAK MRA provides both vascular anatomy and hemodynamic information, which are of great value in clinical assessments (
17,
19), especially venous drainage patterns and possible fistula points. Comparatively, 3D TOF MRA only detected 39% of the venous drainage (
Table 2). Slow flow fistulae or AVM may be easily missed (
Figures 1 -
3) because 3D TOF MRA is a T1-weighted imaging technique for static vascular lesions (
31). In addition, subacute thrombosis within a fistula vein may be misdiagnosed as a vascular lesion (
32) because any high signal intensity on T1 weighted image could be easily presented on 3D TOF MRA (
2,
33).
3D TOF MRA is a technique that mainly depends on the flow and movement of protons in the blood through the imaging plane with a spoiled gradient echo, high flip angle and short TR. The image obtains relaxed inflowing blood as a high signal intensity under a saturated static magnetization background (
1,
2,
27). The final images are reconstructed by MIP with rotation. Thus, vascular anatomy can be shown without contrast medium injection, eliminating the possibility of contrast medium allergic reactions or nephrogenic systemic fibrosis (NSF). Research in the recent years has shown that 3D TOF MRA can be regarded as a valuable tool for the initial diagnosis of dAVF and AVM (
31,
32,
34). They suggested abnormal hyperintensity on the images of 3D TOF MRA, which can provide the diagnosis of a possible fistula point or nidus formation. However, there are still some important shortcomings, including the following: the slow flow fistula may be missed, the possible subacute thrombosis within the fistula vein may show hyperintensity in complete occluded dAVF, and this may be misdiagnosed as fistula flow in follow-up images after treatment (
27). Furthermore, dAVF with retrograde venous flow into the cortical veins may show a large portion of hyperintensity that may obscure the true fistula point or the location of a possible feeding artery. In addition, for primary diagnosis or follow-up of AVM and dAVF, identification of the drainage vein is very important (
35-
37). Thus, lack of hemodynamic information and venous phase information constitute the other drawback of this sequence. For these reasons, although the 3D TOF MRA is a useful method in the initial diagnosis of dAVF and AVMs, lack of dynamic information is a major shortcoming.
The interobserver agreement in 4D-TRAK MRA showed excellent agreement in lesion diagnosis and venous drainage assessment. Although the spatial resolution of 3D TOF MRA may sometimes be better than that of 4D-TRAK MRA (
17), it is still not good enough for AVM nidus or fistula point identification. In other words, slow flow fistulae may be missed, and any hyperintensity may cause false interpretations of 3D TOF MRA. For this reason, the confidence of lesion depiction was lower, as was the interobserver agreement. With regard to the arterial feeder, neither interobserver agreement was excellent. We know that arterial feeders and even the main feeder to vascular lesions can be quite small in size. The relative poor spatial resolution may be the other factor causing artery assessment to be less consentient in 3D TOF MRA and even in 4D-TRAK MRA among readers with different diagnostic experiences (
36). In addition, the capacity of traditional DSA in showing additional small feeders is due to its direct determination of the origin of the arterial feeders by injecting contrast medium into the four supra-aortic vessels, one by one, simply visualizing the nidus or fistula site. As a result, further advances in MRA techniques to improve spatial resolution are key points to be worked out in the future (
30).
Although the diagnostic value and major arterial feeder identification of 3D TOF MRA have gained a certain reliability in current clinical use (
31,
32), vessels with lower flows or smaller sizes may be still easily overlooked (
27,
32). Furthermore, in some of our cases, the possible subacute thrombosis within fistula veins showing hyperintensity in completely occluded dAVF may be regarded as a residual fistula flow (
38). Most importantly, without venous phase image for drainage vein assessment, the diagnostic accuracy of 3D TOF MRA is still far from equal to DSA, which requires the gold standard for characterization of AVM and dAVF (
34). Comparatively, the higher diagnostic accuracy and venous drainage pattern recognized by the sequential arterial and venous phase images of 4D-TRAK MRA makes it far superior to 3D TOF MRA. Therefore, 4D-TRAK MRA is undoubtedly a more reliable tool in diagnosing cerebral AVM and dAVF.
The 4D-TRAK MRA acquired using CENTRA keyhole imaging, a parallel imaging technique and a multiphase acquisition technique, enables a rapid sequential analysis of arteries, capillaries and veins and facilitates the identification of early venous filling or retrograde flow in volumetric studies (
16). The special k-space sampling is mainly divided into two regions: the centrally located k-space, which contributes to image contrast information by more frequent sampling, and the peripherally located regions, which provide high spatial resolution, true acceleration of the sequence acquisition time and fewer observed motion artifacts (
19). Therefore, it can provide sequential arterial and venous phase images for venous drainage evaluation. From the results of our study, the definite lesion location, size, arterial feeder, and venous drainage all had good specificity in diagnosis. This means that the basic Spetzler-Martin grading of AVM (
39), diagnosed by the nidus and venous drainage, and Borden-Shucart grading system of dAVF (
40), mainly identified by the drainage vein, can be mostly diagnosed on 4D-TRAK MRA. Thus, with the aid of 4D-TRAK MRA, sufficient information for clinical therapeutic decision-making and planning can be obtained (
30,
37,
41-
43). Furthermore, this MR sequence requires only 1 minute for acquisition, while conventional DSA requires at least 30 minutes for the whole procedure. Therefore, 4D-TRAK MRA might be a good screening method for people with high clinical suspicions of AVM or dAVF. In short, 4D-TRAK MRA may reduce the necessity of performing conventional DSA for initial diagnosis or post-treatment follow-up in the future.
In our study, we observed that the vascular lesions that could not be correctly diagnosed on 4D-TRAK MRA were mostly small or those with extremely slow flows. This is because the specificity of CENTRA keyhole places emphasis on contrast data (central k-space) rather than on spatial resolution data (peripheral k-space), representing a trade-off in clinical practice between spatial resolution and temporal resolution. Consequently, the small residual nidus or extremely slow flow may cause some difficulties in identification, and traditional DSA may be the only choice for these small lesions. In other words, 4D-TRAK MRA can identify major arterial feeders but may overlook the small ones. Additionally, we also observed that there were identical results on 3D TOF MRA in three parameters of the dAVF assessment (
Table 4). The most reasonable explanation is that vascular lesions with prominent and fast flow venous drainage detected by 3D TOF MRA may be regarded as an early drainage vein. Furthermore, observing early drainage veins indicates a higher possibility of dAVF presence. Therefore, if the drainage vein is not identified, we will not be able to make the diagnosis.
The present study is not without limitations. First, no control group of patients without vascular lesion was established, so observer bias of the reviewers is present. Second, the time interval between MRA examination and conventional DSA may have caused some unpredictable differences between the two imaging modalities, even though the recruited patient population underwent two examinations within one month. Finally, the number of subjects in this study was small, consisting of only 41 patients in total. Subdividing these patients into groups such as AVM vs. dAVF and initial diagnosis vs. follow-up makes the small sample size an even bigger issue. Thus, further studies with larger numbers of patients to confirm the superior clinical results of 4D-TRAK MRA over 3D TOF MRA is needed.
In conclusion, although DSA is still the gold standard (
43) in the diagnosis of cerebral AVM and dAVF, several different less invasive MRA sequences have gained clinical importance in the recent years. TR-MRA provides sequential arterial and venous phase images, making it superior to 3D TOF MRA in diagnostic accuracy. Our results suggest that TR-MRA seems to be a more reliable modality in the identification of cerebral AVM and dAVF.