Are Dynamic Arterial Spin-Labeling MRA and Time-Resolved Contrast-Enhanced MRA Suited for Confirmation of Obliteration following Gamma Knife Radiosurgery of Brain Arteriovenous Malformations?

DISCUSSION

This work presents the use of 2 dynamic MRA techniques based on ASL and gadolinium bolus tracking for confirmation of obliteration of brain AVMs following GKR. The ASL-MRA, CE-MRA, and DSA sequences of 29 patients who underwent follow-up imaging to confirm obliteration of brain AVMs following GKR were blindly and independently assessed by 2 observers. ASL-MRA and CE-MRA individually have limited sensitivity and NPV for detection of residual AVMs after radiosurgery. This is of clinical importance because false-negative investigations could result in a persistent risk of hemorrhage from AVMs in patients thought to have been cured. The combined use of ASL-MRA and CE-MRA, which provide both temporal and spatial information, appears to be a reliable method to confirm/rule out the presence of residual AVMs after radiosurgery. The composite use of dynamic ASL-MRA and CE-MRA in our study showed maximal sensitivity and specificity compared with DSA; this outcome makes this the first study demonstrating satisfactory diagnostic accuracy of MRA for confirmation of obliteration following GKR of brain AVMs. The results of this study support the use of ASL-MRA and CE-MRA as a first-line technique for confirmation of obliteration following GKR, which is of high clinical relevance because this would not only avoid unnecessary DSA examinations for patients with cured AVMs (69% in our study group) but also help rationalize its use in patients with residual AVMs who may need more DSAs for further treatment.

The major accomplishment of using two 4D-MRA sequences is the combination of high temporal and spatial resolution, which is necessary to appreciate the dynamic characteristics of AVMs.¹⁹ AVMs exhibit a high degree of heterogeneity in terms of angioarchitecture and flow dynamics, and even within the same lesion, there may be dramatic and unpredictable differences in terms of vessel configuration and blood flow. This accomplishment is most likely the reason for the disappointing results of previous studies that attempted to detect and fully characterize residual AVMs using either TOF or CE-MRA.^4,5,9,10 If used independently, those MRA sequences are unable to capture all the complexity and heterogeneity of shapes, sizes, and velocities seen on AVMs. However, in combination, the chance of false-negatives is reduced and their combined ability to detect/rule out residual AVMs after GKR is increased. This feature is demonstrated in our study by the visualization of all residual AVMs in at least 1 MRA sequence and the optimal characterization of residual AVMs using structural and dynamic information obtained from both MRA modalities. Such use of multiple sequences for diagnostic purposes is commonplace in radiology, and it is well-accepted that information from multiple sources (ie, T1WI, T2WI, and contrast imaging) may be required to achieve a full diagnosis.

The main limitation of our study is that a separate review of each MRA sequence, to assess their ability to individually confirm AVM obliteration, was not part of the design. This was because multiple studies had previously concluded that individually, all previously used MRA sequences have suboptimal diagnostic accuracy compared with DSA.^4,5,9,10 Also, the review of both MRA sequences separately followed by their combined re-assessment would have resulted in increasing and unpredictable reporting bias. Instead, as part of the combined assessment of both MRA sequences, the observers indicated which of the 2 showed the residual AVM, and this information provided some insight into the diagnostic accuracy of each individual sequence. However, we cannot assume that the outcome would have been the same if each MRA technique were assessed independently because the combined assessment of the 2 is highly likely to have resulted in a degree of crossed reinforcement or reassurance of findings between the individual sequences.

In our study, CE-MRA appeared to have lower diagnostic accuracy by failing to show 2 residual AVMs that were clearly visualized on ASL-MRA and DSA (Fig 2). CE-MRA is prone to motion artifacts, and it relies on single-pass bolus tracking, which contributed to a technically unsatisfactory MRA dataset that was excluded from the analysis. Nonetheless, CE-MRA provided valuable dynamic information for the characterization of residual lesions, in terms of feeding arteries and draining veins, and it can also depict arteriovenous shunting, which was essential in the evaluation of AVM obliteration. CE-MRA was very important in a case in which the residual AVM was not visualized on ASL-MRA (Fig 1), and this case demonstrates how the 2 sequences complement each other, increasing the chances of AVM detection and enabling the characterization of residual AVMs.

Regarding ASL-MRA, to date, no previous studies exist on its use for confirmation of AVM obliteration after radiosurgery. A number of studies have used it, together with ASL perfusion, for assessment of AVMs with promising results, but their value compared with DSA is also still to be fully established.^20⇓-22 ASL is an appealing technique for confirmation of obliteration because venous signal in AVM draining veins can be considered a strong indication of arteriovenous shunting, which is an unequivocal defining element of an AVM. During an ASL acquisition, the arterial blood water is labeled with a radiofrequency pulse proximal to the brain, and it is used as an endogenous contrast agent.^17,23 Under normal physiologic conditions, the time it would take for the labeled water to reach the veins (either via intravascular transport through the microvascular bed or via extravasation into the extravascular compartment and subsequently being picked up in the venous system) is longer than the time between the start of labeling and the readout. Thus, there is normally little detectable signal within the intracranial veins on ASL perfusion images²⁴ or on ASL angiography. Furthermore, decay of the tagged spins in ASL angiography is accelerated by the train of readout excitation pulses, resulting in additional signal reduction more distal into the vascular tree. In AVMs, however, the labeled spins are rapidly shunted directly into the venous circulation, giving rise to high signal intensity in AVM draining veins.²⁵ In our study, ASL-MRA proved critical to the assessment of the response to GKR in 2 cases in which CE-MRA failed to demonstrate the residual lesion (Fig 2). It also provided important information on nidus size and the number of feeding arteries. However, as in other individual MRA sequences, ASL-MRA is, by itself, unable to capture all the possible scenarios of size, flow, and velocity to reliably detect residual AVMs, evidenced by the occurrence of a false-positive in which ASL-MRA failed to show the residual nidus (Fig 1).

In our study, the observers were aided by a very high index of suspicion because they were aware of the location of AVMs at treatment and, therefore, knew where to look for residual lesions. It could be argued that results would have been different if the observers had no indication of the potential AVM location; however, the study was pragmatically designed to replicate the clinical scenario in which DSA examinations are reviewed specifically to confirm obliteration. We performed DSA once obliteration was demonstrated on regular follow-up MR imaging/MRA or after 4 years if no response or only partial response was seen on MR imaging/MRA. This procedure could have introduced a degree of selection bias. Also, we had a relatively small sample size, which is a limitation of the study. The assessment of a larger number of patients is needed to strengthen the power of the results.

Optimization of MRA sequences for further implementation should include individualized time resolution of ASL-MRA, which can be used to better characterize the flow dynamics of residual AVMs. There is also a great potential for improvement of MRA by postprocessing the individual datasets and, through their combination, generating a single product that incorporates the information provided by both sequences. This improvement is still to be accomplished and developers should aim for more sophisticated 4D visualization maps, which enhance the visual experience and facilitate interpretation.