Introduction

The standard microsurgical procedure for treating saccular aneurysms involves ligating the aneurysm neck with a titanium clip. Although the incidence of aneurysm remnants or recurrence after clipping is low, there is substantial evidence supporting the need for routine surveillance imaging after clipping, as aneurysm recurrence or de novo aneurysm formation with subsequent subarachnoid hemorrhage (SAH) can occur [1,2,3,4,5,6,7]. Digital subtraction angiography (DSA) and computed tomography angiography (CTA) are the current standard of care for follow-up imaging of clipped aneurysms (CAs), but they carry the risk of radiation exposure and contrast agent toxicity [8, 9]. Time-of-flight magnetic resonance angiography (TOF-MRA) is an alternative that avoids these risks, but its use as a follow-up imaging tool is limited due to susceptibility artifacts caused by implanted clips [10]. To address these challenges, new MRA sequences with reduced susceptibility artifacts have been developed. Recent studies have shown that pointwise encoding time reduction with radial acquisition (PETRA) subtraction-based MRA (Siemens Healthineers, Erlangen, Germany) is a non-contrast MR technique like TOF-MRA and provides better visualization of adjacent vessels near implanted metals compared to TOF-MRA; however, most studies have focused only on stent-assisted coiled or simply coiled aneurysms, comparing PETRA-MRA with DSA [11,12,13,14,15].

Some studies [16, 17] have compared PETRA-MRA with CTA or TOF-MRA for the follow-up imaging of aneurysms after clipping, and there are a few studies of head to head comparison of PETRA-MRA and DSA as a reference for clipped aneurysms to confirm the diagnostic performance of PETRA-MRA [16, 17]. Therefore, we aimed to validate the diagnostic performance of PETRA-MRA for the follow-up imaging of CA by comparing it with DSA as a reference.

Material and Methods

Patients

The institutional review board examined this retrospective study, and the need for informed consent was waived. In our hospital, brain CTA or TOF-MRA was used as a surveillance imaging in the follow-up of CAs, while DSA was performed at the discretion of the clinician. Since September 2019, PETRA-MRA has been routinely used alongside TOF-MRA for the evaluation of CAs. Patients who underwent both PETRA-MRA and DSA within 6 months for follow-up imaging were retrospectively included from a database spanning from September 2019 to December 2021.

Exclusion criteria encompassed patients who did not undergo either PETRA-MRA or DSA, as well as those lost to follow-up. PETRA-MRA images with poor image quality due to motion artifacts were also excluded to ensure accurate comparisons.

Imaging Acquisition

Images using TOF-MRA and PETRA-MRA were acquired together in a single scan session using a 3‑T MR scanner (Vida, Siemens Healthineers) with a 128-channel head-neck coil. The scan parameters for TOF-MRA were: TR/TE = 21.0/3.69 ms, flip angle = 20°, FOV = 235 × 212 mm, matrix = 384 × 344, voxel size = 0.6 × 0.6 × 0.5 mm3, section thickness = 0.5 mm, compressed sensing factor = 9, bandwidth = 186 Hz/pixel, acquisition time = 5 min 49 s, number of slabs = 7. The following scan parameters were used for PETRA-MRA: TR/TE 5.5/0.07 ms; flip angle 6°; FOV 220 × 220 mm; matrix 256 × 256; radial sampling 33,000 radial spokes; voxel size 0.86 × 0.86 × 0.9 mm3; slice thickness 0.9 mm; NEX 1; and bandwidth 399 Hz/pixel. Both MR sequences were performed without contrast agent. The acquisition time for PETRA-MRA was 6 min 52 s, regardless of the presence or absence of a saturation band. Maximum intensity projections were reconstructed using the system software (Siemens Healthineers). Postprocessing times for PETRA-MRA sequences was less than 5 min.

The DSA images were acquired using a biplane angiographic system (Artis zee biplane, [Siemens Healthineers, Erlangen, Germany]). In all cases, 3D rotational angiographic images were obtained following a standard protocol, and a nonionic contrast agent (Visipaque 270, [GE Healthcare Life Sciences, Buckinghamshire, UK]) was used.

Imaging Analysis

Imaging analysis was performed using the reconstructed images of both MRA and 3D images of DSA. In selected cases, the reconstructed MRA images were independently reviewed by 2 neuroradiologists (SJA and MP) with more than 10 years of experience using a picture archiving and communication system (PACS; Centricity PACS, GE Healthcare). They were blinded to all clinical information of patients except for the location of the clipped aneurysms. In cases of disagreement for evaluation of aneurysm recurrence, consensus was reached.

Visibility of the parent artery and the branch vessels near the clips in TOF-MRA and PETRA-MRA was graded by two readers using a previously published 3‑point scale [16]. Aneurysm remnants or recurrence of CAs on PETRA-MRA were graded according to the following criteria. Based on the Sindou classification [18] a modified 3‑point scale was used to grade aneurysm recurrence or remnant of the CAs: grade 1 was interpreted as complete clipping without recurrence, grade 2 as clipping with suspicious minimal neck, and grade 3 as clipping with definite recurrence or remnant. In addition, a dichotomized scale of absence or presence of aneurysm recurrence or remnant (grade 1 + 2 versus 3) was used.

The 3D-DSA images were graded according to the same scale by an interventional neuroradiologist (SHS) with more than 15 years of experience.

Statistical Analysis

Continuous variables were presented as mean ± standard deviation, while categorical variables were reported as frequencies and percentages. The independent 2‑sample t‑test was used to assess differences for continuous variables, and the χ2-test (or Fisher’s exact test) was employed for categorical variables. Interobserver agreement was evaluated using k‑statistics and interpreted as follows: 0 (no agreement), 0.01–0.20 (slight agreement), 0.21–0.40 (fair agreement), 0.41–0.60 (moderate agreement), 0.61–0.80 (substantial agreement), and 0.81–1.00 (almost perfect agreement) [19]. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of PETRA-MRA were determined using DSA as the reference for assessing aneurysm remnants or recurrence after clipping. Statistical significance was considered for p-values ≤ 0.05. Statistical analyses were performed using SPSS v.19.0 (IBM, Armonk, New York, USA).

Results

Patients and Aneurysm Characteristics

A total of 522 patients who underwent PETRA-MRA between September 2019 and December 2021 were initially included in this study. Among them, 470 patients without follow-up DSA were excluded. From the remaining 52 patients who had both PETRA-MRA and DSA, 18 patients were further excluded due to inadequate visibility caused by motion artifacts. Finally, a total of 34 patients (28 females) with 48 titanium alloy clipped aneurysms were included in the analysis (Table 1). The mean age of the patients was 59 ± 9.6 years. The average follow-up period between operation and subsequent MRA and DSA was 48.7 ± 47.4 months.

Table 1 Demographic characteristics of 34 patients with 48 aneurysms
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The average size of the aneurysms was 4.7 ± 2.2 mm in maximum diameter and 13 patients (38.2%) presented with subarachnoid hemorrhage. In terms of multiple aneurysms 11 patients (32.4%) were identified, with 9 patients having 2 aneurysms each, 1 patient with 3 aneurysms, and 1 patient with 4 aneurysms. The locations of all 48 clipped aneurysms are summarized in Table 1. The average number of clips used per aneurysm was 1.9, with a range of 1–4 clips. The number of clips used was as follows: 1 clip was required in 20, 2 in 16, 3 in 9, and 4 in 3 of the 48 aneurysms.

Visibility of the Parent and Adjacent Arteries around Clips

With PETRA-MRA, both the parent artery and the branching vessels were visible around the clip in 77.1% (37/48) of the CAs, while all vessels were visible in 29.2% (14/48) with TOF-MRA (p < 0.0001, Table 2). In 97.9% (47/48) of PETRA-MRA cases, the parent artery was visible around the clip, while no vessel was visible around the clip in 60.4% (29/48) of TOF-MRA cases. There was an interobserver agreement of 0.56 for the visibility of vessels with clips on PETRA-MRA.

Table 2 Comparison between TOF-MRA and PETRA-MRA for visibility of the parent artery and adjacent arteries near the clip
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Diagnostic Performance of PETRA-MRA for Detection of Aneurysm Remnants or Recurrence

Of the 48 CAs, a total of 14 (29.2%) cases were confirmed as grade 2 or 3 by DSA (Table 3). The mean size of the residual aneurysm was 1.58 ± 0.72 mm, for the 11 cases diagnosed as grade 2 by DSA it was 1.3 ± 0.4 mm and the remaining 3 cases diagnosed as grade 3 were 2.5 ± 0.7 mm (p = 0.0018). Of the 14 cases, 9 cases interpreted as grade 1 on PETRA-MRA were less than 2 mm in size and 5 cases interpreted as grade 2 or 3 were equal to or greater than 2 mm.

Table 3 Characteristics of 14 patients with aneurysm remnants or recurrence confirmed by DSA
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For the detection of aneurysm recurrence or remnants, PETRA-MRA showed an accuracy of 99.2%, sensitivity of 66.7%, specificity of 100%, PPV of 100%, and NPV of 97.8%.

The interobserver agreement between the two readers for PETRA-MRA was 0.45 on a 3-point scale and 0.68 on the dichotomized scale. On a 3-point scale, 9 out of 48 cases (18.8%) showed discordance (Table 4). Of these cases, 8 were interpreted as grade 1 on PETRA-MRA and grade 2 on DSA. The remaining false negative case was interpreted as grade 1 on PETRA-MRA and grade 3 on DSA, which also showed discordance on the dichotomized scale (Fig. 1).

Table 4 Reading between PETRA-MRA and DSA using a 3-grade scale
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Fig. 1
figure 1

False negative (top row) and true positive (middle and bottom rows) cases; TOF-MRA (a, d), PETRA-MRA (b, e), 3D-DSA (c, f) and source image of TOF-MRA (g), PETRA-MRA (h) and DSA (i). In the false negative case (top row), PETRA-MRA showed complete clipping but 3D-DSA confirmed the presence of a 2 mm aneurysm remnant (arrow). Note that the anterior choroidal artery was not visualized on PETRA-MRA. In the middle and bottom rows, both PETRA-MRA (arrow) and DSA readings were consistent and showed a definite aneurysm recurrence or remnant which was larger than 2 mm

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Discussion

In this study, we demonstrated that PETRA-MRA showed an excellent diagnostic performance in detecting aneurysm remnants or recurrence for CAs, with good visibility of the neighboring vessels near the clips, which demonstrated specificity, PPV, NPV, and accuracy rates exceeding 99%, along with a moderate sensitivity. The interobserver agreement of PETRA-MRA readings was moderate on a 3-point scale and substantial on the dichotomized scale. The low interobserver agreement on the 3‑point scale may be due to (1) the diagnostic power of PETRA is likely limited by aneurysm size, and aneurysm remnants smaller than 2 mm in PETRA were not diagnosed as described in this study and (2) the diagnostic criteria for a grade 2 suspicious neck remnant may be ambiguous for the 2 readers for PETRA.

While DSA and CTA are currently the standard of care for follow-up imaging of CAs, TOF-MRA is commonly used as a screening tool for unruptured cerebral aneurysms [8, 20]. Recently, new ultra-short echo time MR sequences such as PETRA-MRA and Silent MRA (GE Healthcare, Milwaukee, USA) have been developed to improve image quality by reducing metal artifacts, highlighting the advantages of MRA [21, 22]. Moreover, PETRA-MRA provided superior visualization of aneurysms with decreased flow dephasing and increased edge sharpness compared to TOF-MRA, which was primarily attributed to suppression of the background tissue and venous flow [23, 24]. Several preliminary studies have been published on the clinical application of PETRA-MRA to reduce metal artifacts in CAs and to identify signals in the vessels around the clip [16, 17, 25]. This study is the first to validate the diagnostic accuracy of PETRA-MRA by head to head comparison with DSA and to determine whether this MRA sequence can be used as an alternative imaging modality for the follow-up of CA.

Van Loon et al. [26] reported that CTA was superior to MRA in aneurysms with titanium clips, and they recommended CTA as the preferred imaging modality for routine surveillance. Kim et al. [27] found that the sensitivity of CTA in detecting residual and recurrent aneurysms was 79–83% compared to 3D DSA; however, CTA is generally less accurate than DSA, particularly for small aneurysms (< 2 mm), cases with multiple or cobalt alloy clips, aneurysms located on small parent vessels or those near bony structures [27,28,29]. Xiang et al. [30] suggested that the sensitivity and specificity of TOF-MRA in detecting the aneurysm remnants after clipping were 50.0% and 100%, respectively. They observed that the artifacts in TOF-MRA prevented the detection of the small residual neck in 3 CAs as visualized on DSA. In our study, PETRA-MRA demonstrated a sensitivity of 66.7% and specificity of 100% in detecting aneurysm recurrence or remnants after clipping, which were higher than those of TOF-MRA.

Our study demonstrated that approximately 78% of the cases had excellent visibility of all adjacent vessels near the clips, and more than 95% of the parent vessels were visible, which is superior to previous studies. Some authors have suggested that approximately 84% of the parent arteries around clips were visible on PETRA-MRA or Silent MRA [16, 25]. Moreover, previous studies have reported lower visibility rates for all neighboring vessels near the clips, ranging from 53% to 69% compared to this study [16, 17]. In this study, most of the parent arteries around the clips are visible, making it easier to evaluate remnants or recurrence of the peri-clip lesion; however, the branching vessels distal to the clips were not visible in 10 cases, with 50% of those cases treated with more than 3 clips. Also PETRA-MRA could be influenced by factors such as the number of clips used and the orientation of the clips relative to the magnetic field [16, 31].

Of 14 positive lesions on DSA, the size of the aneurysm remnant or recurrence was less than 2 mm in 9 discordant cases, which were interpreted as grade 1 on PETRA-MRA by a 3-point scale. Of these discordant cases, 8 cases were interpreted as grade 2 on DSA and 1 case as grade 3, which was a clipped aneurysm involving the anterior choroidal artery (Fig. 1). In the 5 concordant cases the aneurysms were larger than 2 mm. Notably, two CAs of more than 2.5 mm were initially suspected of being aneurysm recurrences on PETRA-MRA, which was located in the bifurcation of the middle cerebral artery. Although the size of the residual aneurysm may be an important factor in the diagnostic performance of PETRA-MRA [32] it is important that aneurysm recurrence or remnants larger than 2 mm can be diagnosed with PETRA-MRA in clipped aneurysms.

Limitations

Our study has several limitations that should be considered. First, it had a retrospective design, which introduces the possibility of selection bias. Although we had many PETRA-MRA cases during the study period (more than 500), only a limited number of cases could be included in this study due to the lack of follow-up DSA and inconsistent intervals between DSA and PETRA-MRA, leading to a potential selection bias. Second, approximately 30% of the 52 subjects in this study were excluded due to poor image acquisition caused by motion artifacts, especially in the early stages of implementation of the new MR sequence with its longer scan time. In general, TOF-MRA has better image quality than PETRA-MRA [16], and to improve the background noise and the low signal-to-noise ratio in PETRA-MRA You et al. [33] have proposed the use of a deep learning model. Third, it was difficult to differentiate between an aneurysm remnant and a recurrent aneurysm, which may occur in CAs during the 48-month follow-up period. Furthermore, this would require a review of the operative records, which unfortunately was not included in this study; however, two aneurysms larger than 2.5 mm were diagnosed as recurrences and treated with coil embolization.

Conclusion

This retrospective study demonstrates that PETRA-MRA provides good visibility of adjacent vessels near the clips and high diagnostic accuracy in detecting aneurysm remnants or recurrence in CAs. These results suggest that PETRA-MRA may be a valuable imaging tool for the surveillance and follow-up of CAs; however, further studies are needed to validate these findings in a prospective large cohort study, which will strengthen PETRA-MRA as a reliable alternative to other imaging modalities for the follow-up after clipping.