Evaluation of 4D Vascular Flow and Tissue Perfusion in Cerebral Arteriovenous Malformations: Influence of Spetzler-Martin Grade, Clinical Presentation, and AVM Risk Factors

Discussion

The results of this study demonstrate the potential of 4D flow and DSC perfusion MR imaging for the comprehensive evaluation of macro- and microvascular hemodynamics in cerebral AVMs. 4D flow MR imaging provided 3D visualization of complex AVM arterial feeding and venous draining patterns and offered quantitative flow characterization of large intracranial AVM vessels. DSC PWI was used to characterize the relative differences in microvascular perfusion parameters. Our findings demonstrate the association of the SMG classification with flow parameters and also reveal significant relationships between macrovascular flow and perinidal tissue perfusion but indicate no significant association of AVM flow or perfusion parameters with symptomatic and anatomic risk factors.

Cerebral AVMs are highly heterogeneous and complex lesions that preclude standardized clinical protocols and uniform paradigms for risk stratification and treatment planning. Initial results from A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) have questioned the benefit-to-risk ratio of interventional therapy versus medical management in unruptured AVMs.¹⁶ Previous studies indicated that perinidal tissue perfusion and flow dynamics in the AVM feeding and draining systems play an important role in assessing the intra- and postoperative hemorrhagic risk.^17,18 Hence, patient- and AVM-specific risk stratification with individualized AVM hemodynamic evaluation may be an increasingly important analysis required to demonstrate a benefit of embolization or surgical treatment in high-risk AVMs.

A growing number of AVM risk factors have been demonstrated to be associated with increased risk of future hemorrhage, such as prior intracranial hemorrhage,^1,19 a single draining vein,¹⁹ flow-induced aneurysms,²⁰ and deep location.^1,21 However, the mechanisms of how these factors confer increased hemorrhagic risk remain unclear, with a paucity of data on the role of quantitative AVM hemodynamics. Illies et al²² reported that a previous intracranial hemorrhage was the only risk factor associated with a significant increase of the relative transit time. In our study, we observed no direct connection between AVM hemodynamic parameters and a history of intracranial hemorrhage based on a relatively small sample size. In addition, our findings revealed no significant association of AVM flow or perfusion parameters with seizure history and other anatomic risk factors.

An early 4D flow study by Chang et al⁷ identified significantly higher time-averaged flow and velocity in the ipsilateral arteries compared with normal contralateral vessels. Similar to their findings, our results demonstrate significantly higher peak velocity and blood flow in the feeding arteries compared with normal contralateral arteries. In addition, our results demonstrate that the SMG directly correlates with arterial flow parameters: The major feeding arteries in high-grade AVMs had significantly higher peak velocities and blood flow in comparison with low-grade AVMs. In addition to SMG, correlations were also identified between AVM nidal volume and cumulative arterial/venous blood flow, indicating that nidal size in the SMG grading system is presumably the dominating factor responsible for different AVM hemodynamics.

A subset of the patients enrolled in this study (AVM 1–14) have been included in a previously reported pilot 4D flow MR imaging study.⁶ The present study included additional recruited patients, refined flow-quantification analysis, and a combination with DSC perfusion MR imaging that was not described in the previous study. In the previous study, a direct relationship between SMG and increased blood flow velocities was found only for draining veins by visual grading of time-integrated pathlines on a 3-point scale (0: <0.25 m/s, 1: <0.5 m/s, 2: >0.5 m/s).⁶ Reanalysis of these data by using regional flow quantification as used in this study demonstrated the following arterial feeding and venous draining peak velocities in 3 SMG groups: SMG = 1 (0.68 ± 0.29 m/s; 0.32 ± 0.13 m/s), SMG = 2 (0.79 ± 0.23 m/s; 0.38 ± 0.16 m/s), and SMG > 3 (0.97 ± 0.54 m/s; 0.50 ± 0.24 m/s). In comparison, the previously used visual velocity grading resulted in SMG = 1 (1.7 ± 0.6; 0.6 ± 0.6), SMG = 2 (1.4 ± 0.5; 0.8 ± 0.8), and SMG > 3 (1.6 ± 0.5; 1.2 ± 0.6). These results indicate that visual grading analysis agreed with quantitative measures for venous velocities but resulted in lower arterial velocities in group SMG = 2 compared with group SMG = 1. In contrast, quantitative analysis showed consistently increased arterial velocities with increasing SMG. The discrepancy may be caused by a different magnitude of velocities in the arterial (0.88 ± 0.44 m/s) and venous (0.43 ± 0.21 m/s) systems. The previously used visual grading method may thus not have allowed accurate arterial velocity measurement for arterial velocities of >0.5 m/s.

Fast arterial-to-venous blood flow velocities in cerebral AVMs present a great challenge for the quantification of arteriovenous shunting with conventional imaging techniques. It is problematic to quantify arteriovenous shunting simply on the basis of absolute arterial or venous blood flow velocities without consideration of the complex and heterogeneous nidal vascular network. DSA, time-resolved contrast-enhanced MRA, and arterial spin-labeled MR imaging have been shown to provide improved quantification of arteriovenous shunting measured with venous arrival time or arterial-to-venous transit time.^15,23,24

A previous DSC PWI study demonstrated AVM steal based on significantly higher Hi/Hc ratios of CBF and CBV in 19 patients with AVMs in comparison with healthy subjects.¹⁴ Fiehler et al²⁵ reported decreased perfusion ratios between affected and nonaffected hemispheres in the MCA and PCA territories accounting for AVM steal. In our study, there were significantly lower perinidal CBF and CBV ratios compared with the remote ratios indicating presence of perinidal hypoperfusion (“AVM steal”). Our perfusion imaging findings were not affected if the 2 ruptured AVMs (AVM-5 and AVM-7) were excluded from the analysis. Flow voids were observed within a high-flow AVM nidus (Fig 2, thin white arrows) due to spin-echo PWI. The signal voids may be alleviated by increasing section thickness and shortening the TR.

A major limitation of this study is the small number of patients with AVMs (n = 17), which underlines the relatively rare pathology of cerebral AVMs. Nevertheless, to our knowledge, this is the largest cohort to date for quantitative evaluation of flow parameters in both AVM arterial and venous systems as well as microvascular brain tissue perfusion. Future studies with larger patient cohorts and healthy control groups are warranted to increase the statistical power and further clarify the relevance of macrovascular flow and microvascular tissue perfusion in cerebral AVMs.

Another limitation related to 4D flow MR imaging is its inability to capture the wide range of velocities in cerebral AVMs (ie, fast feeding artery flow versus slow venous flow). Dual velocity encoding is promising to improve the velocity-to-noise ratio for vascular flow quantification.²⁶ In addition, small vessels (eg, feeding arteries and draining veins with diameters of <3 mm) were difficult to visualize and quantify with the current 4D flow technique due to limited spatial resolution, which may be improved by advanced imaging accelerating techniques to increase spatial resolution while keeping total scan times at acceptable levels.²⁷ Moreover, the AVMs included in this study had a different number of feeding and draining vessels, which may bias the statistical results for the peak velocities and blood flow.

The perfusion method used in this study has been successfully applied in the evaluation of brain tumor,¹⁰ but it was only validated against the reference standard (PET) for gradient-echo PWI.²⁸ In addition, a wide variability in contralateral white matter CBF values was reported in the presence of vascular pathology.²⁹ Thus, we were cautious to use the values in our study as quantitative perfusion measurement in cerebral AVMs without further validation. Instead, the relative perfusion ratios between the affected and nonaffected hemispheres were calculated to characterize the potential perfusion disturbance. Moreover, although a single section with the largest nidal dimension was considered to represent the most significant hemodynamics in cerebral AVMs,¹⁴ 3D assessment of brain tissue perfusion would provide better characterization of microvascular hemodynamic disturbance in cerebral AVMs.²²