Assessment of stent change after symptomatic intracranial artery stenosis using 3D high-resolution vessel wall imaging: A comparative study

doi:10.21203/rs.3.rs-1996040/v1

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Assessment of stent change after symptomatic intracranial artery stenosis using 3D high-resolution vessel wall imaging: A comparative study

https://doi.org/10.21203/rs.3.rs-1996040/v1

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Purpose

This study aimed to assess stent lumen and vessel wall changes using 3D high-resolution vessel wall imaging (HR-VWI) in patients with intracranial atherosclerotic arterial stenosis after stenting.

Patients and Methods:

We followed up 33 patients after stenting for symptomatic intracranial arterial stenosis using 3D HR-VWI (pre- and post-contrast T1 weighted images [T1WI]), time-of-flight (TOF) magnetic resonance angiography (MRA), and digital subtraction angiography (DSA). Two neuroradiologists measured the in-stent restenosis degree on three modalities. The linear association of stenosis measurements obtained by three different modalities was determined through Spearman’s correlation analysis. Between-reviewer agreement regarding the stenosis degree on HR-VWI was evaluated using the intraclass correlation coefficient (ICC). Further, we evaluated stent wall characteristics, including wall changes and enhancement on pre- and post-contrast T1WI images, respectively.

Results

All patients presented signal loss on TOF MRA at the stenting location. Eleven patients showed in-stent stenosis, with the stenosis degree ranging from 19–100% (occlusion). There was a strong correlation between the in-stent stenosis degrees on HR-VWI and DSA. There was excellent between-reviewer agreement in the stenosis degree (ICC: 0.97). Among the 11 patients, 9 patients presented with vessel wall thickness and enhancement while 2 patients showed intraluminal thrombosis with high-signal filling in the lumen on 3D HR-VWI.

Conclusions

The stenosis degree measured on 3D HR-VWI was consistent with the gold standard DSA. In patients with in-stent stenosis, 3D HR-VWI can reveal the restenosis cause to guide subsequent treatment.

intracranial arterial stenosis

stent

in-stent stenosis

3D high-resolution vessel wall imaging

lumen

vessel wall

Atherosclerotic intracranial arterial stenosis is among the most common stroke causes and is associated with an increased recurrent stroke risk [1]. It is mainly treated through aggressive medical therapy and stenting [2]. Stent placement can reduce stroke recurrence in patient’s refractory to aggressive medical treatment. Recent new stents, including the Enterprise stent, have been clinically used and are technically feasible with a relatively low complication rate for treating complex symptomatic intracranial atherosclerotic arterial stenosis [3].

In patients who have undergone medical or endovascular treatments, especially those with recurrent symptoms, imaging is crucial for diagnosis. Moreover, endovascular intervention may be indicated in case of recurrent high-grade stenosis. Noninvasive imaging modalities, including magnetic resonance angiography (MRA) and computed tomography angiography (CTA), are not optimal for assessing post-stenting vascular status since the yielded images have a suboptimal spatial resolution; moreover, the images are degraded by metal artifacts induced by the intracranial stent. Although digital subtraction angiography (DSA) is the gold standard for assessing intracranial arteries, it may be inappropriate for follow-up imaging of asymptomatic patients after long-term stenting given its invasive nature and the risk of procedure-related stroke [4].

High-resolution vessel wall imaging (HR-VWI) can determine the arterial wall structure and quantify the stenosis degree for patients with intracranial atherosclerotic arterial stenosis. A case report by Shi et al. showed that 2D HR-VWI had clinical utility as an in vivo modality for assessing the lumen and walls of the middle cerebral artery after Wingspan stenting [5]. However, compared with 2D sequence, 3D HR-VWI allows whole-brain coverage, higher spatial resolution, higher signal-to-noise ratio, and isotropical reformatting in multiple planes [6]. This study aimed to assess stent lumen and vessel wall changes using 3D HR-VWI in patients with intracranial atherosclerotic arterial stenosis after stenting.

Study population

This was a retrospective study. The requirement for a written informed consent was waived due to the retrospective nature of the study and local ethical committee granted exemption from requiring informed consent.

Between September 2013 and December 2021, patients who underwent intracranial stenting due to symptoms intracranial artery stenosis were included in this analysis. The inclusion criteria were as follows: (1) patients who underwent post-stenting follow up with time-of-flight (TOF), 3D HR-VWI, and DSA; (2) having HR-VWI scanned on 3 Tesla magnetic resonance imaging (MRI) with a 3D sequence; (3) 3D HR-VWI including pre- and post-contrast T1WI sequences; (4) having a ≤ 1-week interval from 3D HR-VWI to DSA; and (5) having sufficient image quality of 3D HR-VWI for evaluation. Patients were excluded if they had any of the following conditions: (1) the interval between 3D HR-VWI and DSA was longer than 1 week; (2) inadequate images quality, eg, motion artifact obscuring lumen and vessel wall boundaries.

MRI protocol

All the included patients underwent scanning using a 3.0T whole-body MRI system (Skyra, Siemens Healthcare, Erlangen, Germany) using a 20-channel head/neck coil. The 3D TOF sequence was scanned in the axial plane (repetition time [TR]/echo time [TE] = 21/3.43 msec, field of view [FOV] = 181 × 200 mm, slice thickness = 0.7 mm, number of slices = 144, and matrix = 331 × 384).

3D HR-VWI was acquired in the sagittal plane using a spatially nonselective excitation, including pre- and post-contrast T1WI, with the following parameters: T1-weighted fast spin-echo, 0.5 mm; isotropic resolution, 180 × 180 mm; FOV, 360 × 360 matrix; 240 slices; echo train length, 60; TR/TE = 900/5.6 msec; 5/8 partial Fourier in the slice direction; and generalized autocalibrating partial parallel acquisition factor 2 in the phase-encoding direction. The same 3D HR-VWI sequence was repeated immediately after intravenous administration of 1.5 mmol/kg gadolinium (Gadovist; Bayer Schering Pharma).

DSA protocol

DSA was performed using the Artis zee Biplane angiographic system (VC14; Siemens, Erlangen, Germany). We performed a 5-s DSA acquisition protocol with injection of the contrast agent Ultravist (Bayer Healthcare, Berlin, Germany) at a rate of 3 ml/s. During the 5-second acquisition after a 1-s delay, a 200° rotation of the C-arm was performed to yield 133 frames. We used the following parameters: FOV = 320 × 320 mm² and matrix =1024 × 1024. Standard anteroposterior, oblique, and lateral views were obtained in all patients.

Image Analysis

The in-stent stenosis degree was measured on TOF-MRA, 3D HR-VWI (pre-contrast), and DSA based on the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial [7]. Stenosis% =[1-Dstenosis/Dnormal]×100%, Dstenosis is the diameter of the lumen at the stent site, and the Dnormal is the diameter of the lumen at the proximal normal segment. Stenosis measurements were independently performed by two neuroradiologists (both with > 8 years of experience) with an electronic caliper using DICOM reading software (General Electric Advantage Workstation, GE Healthcare, Milwaukee, WI).

Moreover, vessel wall characteristics, including stenting wall changes and enhancement on pre- and post-contrast T1WI images, respectively, were independently evaluated by two neuroradiologists (both with > 8 years of experience). Stenting wall changes on pre-contrast T1WI images were compared with those of normal intracranial arteries. Stenting vessel wall enhancement was defined by the wall signal on post-contrast T1WI images being higher or equal to that of the normal intracranial arterial walls. Regions of interest (ROIs) were drawn on the stenting vessel and normal arterial walls; moreover, we compared the maximal and average signal intensities of the stenting vessel and normal atrial walls, respectively.

Statistical Analysis

Statistical analyses were performed using MedCalc software (Mariakerke, Belgium). Spearman’s correlation analysis was used to determine the linear association among stenosis measurements yielded from three different modalities. The intraclass correlation coefficient (ICC) was used to evaluate between-reviewer agreement regarding the in-stent stenosis degree on HR-VWI.

From an initial cohort of 158 patients, 106 patients did not have 3D HR-VWI follow up image, 15 patients had long interval from 3D HR-VWI to DSA, and 4 patients had bad image quality due to motion artifact. Thirty-three patients (27 males, average age: 60.97 years) who met the inclusion and exclusion criteria were included in this analysis. Among 33 patients included in our analysis, 11, 9, and 13 patients underwent stent placement on the basilar artery, vertebral artery, and middle cerebral artery, respectively. Four patients underwent post-stenting follow up using HR-VWI, TOF, and DSA more than or equal to twice after stenting. The interval between stent placement and MRI scanning ranged from 3 to 36 months (mean: 10.8 months). Moreover, the average interval between post-stenting DSA and MRI was 4.5 days.

No significant stenosis was observed on the location of stent for 22 patients both on 3D HR-VWI and regular follow up DSA. Eleven patients showed in-stent stenosis on the following up images. All patients had signal loss on TOF MRA at the stenting location. Consequently, the in-stent stenosis degree could not be evaluated on TOF MRA. Eleven patients presented with a degree of in-stent restenosis ranging from 19–100% (occlusion). Furthermore, among patients with in-stent stenosis, 3D HR-VWI revealed vessel wall thickness and enhancement in 9 patients, as well as intraluminal thrombosis with high-signal filling in the lumen for 2 patients.

In the 18-month follow-up of one patient, DSA revealed mild stenosis (30%); however, 3D HR-VWI performed on the next day did not reveal stenosis. CTA on same day with DSA also did not reveal any stenosis (Fig. 1). There was a strong correlation between the in-stent stenosis degrees obtained by HR-VWI and DSA (r = 0.95, P ༜ 0.0001). There was excellent between-reviewer agreement in the stenosis degree, with an ICCs of 0.97 (Fig. 2). Other than stent changes, 3D HR-VWI also revealed atherosclerotic plaques of other intracranial arteries in 28 patients.

Table 1 presents the stenting wall changes and vessel wall enhancement on pre- and post-contrast T1WI images for patients with in-stent stenosis. Other than the stenting changes, HR-VWI also revealed atherosclerotic plaques of other intracranial arteries in nine patients.

Table 1

Clinical and imaging characteristics of patients with in-stent stenosis
Patient No.	Sex	Age	Location	Stent type	Time interval between stenting and HR-VWI	Stenosis degree		HR-VWI change
Patient No.	Sex	Age	Location	Stent type	Time interval between stenting and HR-VWI	DSA	HR-VWI	T1WI	T1WI + C
1	Male	72	BA	Enterprise	3 months	19%	21%	Wall thickness	Wall thickness and enhancement
2	Male	64	BA	Wingspan	12 months	100%	100%	High signal filling in the lumen	High signal filling in the lumen
2	Male	64	BA	Wingspan	18 months	30%	0%	normal	normal
3	Mae	52	BA	Solitaire	36 months	38%	35%	Wall thickness	Wall thickness and enhancement
4	Male	71	BA	Solitaire	3 months	62%	60%	Wall thickness	Wall thickness and enhancement
5	Male	59	Left VA	Enterprise	3 months	36%	39%	Wall thickness	Wall thickness and enhancement
5	Male	59	Left VA	Enterprise	8 months	64%	60%	Wall thickness	Wall thickness and enhancement
6	Male	40	Right VA	Wingspan	3 months	100%	100%	High signal filling in the lumen	High signal filling in the lumen
7	Male	76	Right MCA	Enterprise	12 months	69%	67%	Wall thickness	Wall thickness and enhancement
8	Male	61	Left MCA	Enterprise	3 months	88%	86%	Wall thickness	Wall thickness and enhancement
9	Male	60	Right VA	Enterprise	24 months	51%	53%	Wall thickness	Wall thickness and enhancement
10	Male	73	BA	Enterprise	3 months	64%	60%	Wall thickness	Wall thickness and enhancement
11	Male	72	BA	Enterprise	30 months	52%	54%	Wall thickness	Wall thickness and enhancement
Note: MCA, middle cerebral artery; BA, basilar artery; VA, vertebral artery

This preliminary study employed 3D HR-VWI to evaluate in-stent stenosis and post-stenting vessel wall changes in 33 patients. We observed consistency between the stenosis degree measured on 3D HR-MRI and the gold standard DSA. Furthermore, among patients with in-stent stenosis, 3D HR-VWI revealed vessel wall thickness and enhancement in 9 patients, as well as intraluminal thrombosis with high-signal filling in the lumen for 2 patients. Other than stent changes, 3D HR-VWI also revealed atherosclerotic plaques of other intracranial arteries in 28 patients.

Despite aggressive medical treatment, the recurrent stroke risk of intracranial atherosclerotic stenosis may be as high as 12.2%-20.4% [8–10]. The recurrent stroke risk among patients with severe symptomatic intracranial stenosis (≥ 70%) may be as high as 23%.[11] The SAMMPRIS trial reported that aggressive medical management was superior to percutaneous transluminal angioplasty and stenting using the Wingspan stent system. However, the WEAVE results suggested that the poor clinical outcomes observed in the SAMMPRIS trial were not primarily attributed to stent problems but rather to a combination of inexperience among interventionalists, poor patient selection, and unestablished standards of practice in intracranial stenting. Therefore, stenting remains a major endovascular treatment technique and is widely clinically used for patients with intracranial arterial stenosis, especially those refractories to aggressive medical treatment.

Post-stenting imaging follow-up is crucial, especially for patients presenting recurrent symptoms despite treatment. A systematic review and meta-analysis by Peng et al. reported a negative correlation of the in-stent restenosis rate with the imaging follow-up rate given that the latter is reflective of the overall patient compliance with physicians’ suggestions.[12] DSA is the most commonly used clinical follow-up method. However, given its invasive nature, DSA is not considered for follow-up until patients develop new-onset post-stenting symptoms. Although traditional noninvasive imaging modalities can accurately measure the intracranial artery stenosis degree, they are not appropriate for evaluating post-stenting lumen changes. Moreover, we found that all patients had signal loss on TOF MRA at the stenting location. Noninvasive and effective methods are required for regular follow-up of patients after intracranial stenting.

3D HR-VWI can accurately measure the lumen stenosis degree of intracranial arteries [13]. However, the utility of 3D HR-VWI in post-stenting lumen evaluation remains unclear. We observed a strong correlation in the in-stent stenosis degree between HR-VWI and DSA; moreover, it showed excellent between-reviewer agreement. 3D HR-VWI can accurately assess post-stenting lumen changes. At the 18-month follow-up, one patient showed mild stenosis (30%) on DSA; however, 3D HR-VWI after one day showed no stenosis. However, the stenosis indicated by DSA may have been a swirling artifact of blood flow rather than true stenosis. The hypothesis was verified by CTA on the same day with DSA. In patients with in-stent stenosis, 3D HR-VWI can also evaluate the stenosis causes. We observed wall thickness and enhancement in nine patients with in-stent stenosis; moreover, two patients had stenosis caused by intraluminal thrombosis with high-signal filling in the lumen. Besides stent changes, HR-VWI revealed atherosclerotic plaques of other intracranial arteries in 28 patients.

This study has several limitations. First, this study had a limited sample size even though HR-VWI showed potential ability in evaluating both post-stenting lumen and vessel wall changes. There is a need for large-scale prospective studies to evaluate the utility of HR-VWI after stenting. Second, the interval between stenting and MRI scanning ranged from 3 to 36 months. Further studies should monitor dynamic changes of the arterial lumen and wall with regular follow-up 3D HR-VWI. Finally, we did not evaluate pre-stenting vessel wall changes. Comparing pre- and post-stenting vessel wall changes may help distinguish the stent and lesion effects. There is a need for future large-scale studies to evaluate the pre- and post-stenting 3D HR-VWI changes.

Our study showed consistency in the stenosis degree measured on 3D HR-VWI and the gold standard DSA. Furthermore, for patients with in-stent stenosis, 3D HR-VWI could reveal the stenosis cause, which could provide guidance for subsequent treatment.

Acknowledgements

Not applicable.

Author contributions

BT: Study concepts; Study design; Data analysis and interpretation; Statistical analysis; Manuscript preparation. BX: Study concepts; Study design; Data acquisition; Statistical analysis; Manuscript preparation. QQK: Study concepts; Study design; Quality control of Data and algorithms; Data analysis and interpretation; Statistical analysis; Manuscript preparation. XT: Quality control of Data and algorithms; Data analysis and interpretation. CWS: Study design; Manuscript review. JPL: Study design; Manuscript review. DS: Study design; Manuscript editing.

Funding

This research is founded by the Medical Guidance Project of the Shanghai Science and Technology Commission (1941196500) and the Nature Science Foundation of Shanghai(21ZR1479300).

Availability of data and material

The data that support the findings of this study are available from the corresponding author, Jianping Lu, upon reasonable request.

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the Changhai hospital of Shanghai’s ethical committee for studies in humans. All methods were carried out in accordance with relevant guidelines and regulations. The requirement for a written informed consent was waived due to the retrospective nature of the study and the Changhai hospital of Shanghai’s ethical committee granted exemption from requiring informed consent.

Consent for publication

Not applicable.

Competing interest

The authors declare that they have no conflict of interest.

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No competing interests reported.

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Assessment of stent change after symptomatic intracranial artery stenosis using 3D high-resolution vessel wall imaging: A comparative study

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