Jianjian Zhang1, Xiao Li1, Yang Song2, and Huilin Zhao1
1Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 2MR Research Collaboration Team, Siemens Healthineers Ltd. Shanghai, Shanghai, China
Synopsis
Keywords: Vessel Wall, Cardiovascular
Motivation: Atherosclerotic proteins have been implicated with inflammation and remodeling of aneurysm wall. Both aneurysm wall enhancement (AWE) and irregular pulsation have been suggested as potential candidates for intracranial aneurysms (IAs) instability.
Goal(s): To explore the association between atherosclerotic proteins and AWE and irregular pulsation.
Approach: Using vessel wall MRI and four-dimensional computed tomography angiography
Results: We found higher level of serum Lp(a) (Lipoprotein[a]) was significantly associated with increased wall enhancement and irregular pulsation of IAs (both p<0.05)
Impact: This study
established a link between atherosclerotic proteins and AWE and irregular
pulsation, inflammation and wall remodeling.
INTRODUCTION Intracranial
aneurysms (IAs) are relatively common life-threatening diseases with a
prevalence of 3%-5% in adults1. Several imaging
markers for unruptured IAs instability have been explored and aneurysm wall
enhancement (AWE) as identified by contrast-enhanced vessel wall MRI (VW-MRI) has
also been reported as a marker of unstable IAs2. Another potential
novel imaging marker of aneurysm vulnerability is irregular pulsation detected
by four-dimensional computed tomography angiography (4D-CTA), which may
represent a focal weakening of the aneurysm wall3. Current studies
found atherosclerotic proteins might have a pivotal
effect on the inflammation and remodeling of aneurysm wall4. But the association between AWE and irregular
pulsation and the effect of atherosclerotic proteins on the two risk factors is
still unknown and our study aims to investigate this open question.
METHODS This retrospective study included consecutive
patients with IAs who underwent 4D-CTA and VW-MRI between January 2018 to July
2022. The values of serum Lp(a) (Lipoprotein[a]), HDL (high-density lipoprotein), LDL (low-density lipoprotein),
and total cholesterol levels within 30 days of diagnosis were collected. 4D-CTA
was performed on a 320-detector row CT scanner (Aquilion ONE VISION, Canon
Medical System Corporation, Otawara, Japan). Vessel wall MRI was performed on a
3.0T MR scanner (Prisma, Siemens Healthcare or Ingenia, Philips Healthcare or Prisma).
The imaging protocols for MR scanning on Ingenia and Prisma were as
follows respectively: 1) T1WI volume isotropic turbo spin-echo acquisition (T1-VISTA)
sequence with following parameters: TR/TE 800/20msec, number of slices 80,
field of view 250mm×162mm, voxel size 0.6mm×0.6mm×0.6mm, acquisition matrix
416×269, and scan time 5 minutes 2 seconds. 2) T1-weighted 3D black-blood fast
spin echo with variable flip angle trains (SPACE) sequence with following
parameters: TR/TE 1000/15msec, number of slices 240, field of view 193mm×
193mm, voxel size 0.6mm× 0.6mm× 0.6 mm, acquisition matrix 320× 320, and scan
time 9 minutes 13 seconds. Post-contrast VW-MRI sequence was acquired 5 minutes
after Gadolinium-based contrast agent (Magnevist, Bayer Healthcare, Berlin,
German) injection (with a dose of 0.1 mmol/kg, at a rate of 1.5ml/s). Geometric and morphologic parameters
were measured and the presence of irregular pulsation (defined as a temporary focal
protuberance ≥1 mm on more than three successive frames) was identified on
4D-CTA movies6. AWE was
estimated on VW-MRI and classified as 4 grades (grade 0 for none or questionable
focal trace enhancement, grade 1 for focal thick [<1mm]
enhancement, grade 2 for thin [maximum thickness, ≤1 mm] circumferential wall
enhancement, or grade 3 for thick [maximum thickness, ≥1 mm] circumferential
wall enhancement)7. The association between
atherosclerotic proteins and AWE and irregular pulsation was analyzed.
RESULTS One hundred and thirty-one patients with 131 saccular
IAs were included in this study. Irregular pulsation was observed in 38.2% (50/131)
of IAs. Among 131 aneurysms, 63 (48.1%) were enhancing; 21(16.0%) were grade 1,
18 (13.7%) were grade 2, and 24 (18.3%) were grade 3. There was a significantly
strong correlation between AWE
and irregular pulsation (phi coefficient=0.537,
p<0.001). IAs with irregular pulsation showed much higher levels of Lp(a)
compared with those without irregular
pulsation (median [interquartile range], 135.6 [43.5–328.9] versus 74.2 [35.9–171.0],
P=0.029). similarly, IAs with enhacement showed much higher levels of Lp(a)
compared with those without enhancemnet
(median [interquartile range], 137.3 [44.6–322.9] versus 69.2 [25.5–137.4], P=0.001).
DISCUSSION Recent studies have showed both AWE and irregular
pulsation were promising for identification of unstable aneurysms. This study
demonstrated a strong positive correlation between Lp(a) and AWE and irregular pulsation. Lp(a)
was reported to have possible proatherogenic and proinflammatory functions in
the arterial wall5, which might explain its association with AWE. Persistent
inflammation of aneurysm wall involves increased elastic lamina breakdown and
may thereby cause focal weakening of the wall, perhaps explaining the formation
of irregular pulsation. Further research is still needed, however, to study the
association between Lp(a) and irregular pulsation and AWE.
CONCLUSION Higher levels of Lp(a) were significantly
associated with increased wall
enhancement and irregular pulsation. A larger study is needed to confirm these
findings.Acknowledgements
No acknowledgement found.References
1. Hackenberg K, Hanggi D, Etminan N. Unruptured
Intracranial Aneurysms. Stroke 2018;49(9):2268-2275.
2. Vanrossomme AE, Eker OF, Thiran
JP, Courbebaisse GP, Zouaoui BK. Intracranial Aneurysms: Wall Motion Analysis
for Prediction of Rupture. AJNR Am J Neuroradiol 2015;36(10):1796-802.
3. Edjlali M, Guedon A, Ben HW,
Boulouis G, Benzakoun J, Rodriguez-Regent C, Trystram D, Nataf F, Meder JF,
Turski P and others. Circumferential Thick Enhancement at Vessel Wall MRI Has
High Specificity for Intracranial Aneurysm Instability. Radiology 2018;289(1):181-187.
4. Ishii D, Zanaty M, Roa JA, Li L, Lu Y,
Sabotin R, Allan L, Samaniego EA, Hasan DM. Concentration of Lp(a)
(Lipoprotein[a]) in Aneurysm Sac Is Associated With Wall Enhancement of
Unruptured Intracranial Aneurysm. Stroke. 2021 Apr;52(4):1465-1468.
5. Rawther T, Tabet F. Biology,
pathophysiology and current therapies that affect lipoprotein (a) levels. J Mol
Cell Cardiol. 2019 Jun;131:1-11.