ThibaultAGRIPNIDIS, Neuroradiologist, Timone Hospital, AP-HM, Marseille, France
20 February 2025
I would like to thank Shun et al(1) for their very relevant work in assessing the added value of vessel wall imaging in auto-immune rheumatic diseases for the etiology of intracranial artery stenosis. High resolution wall imaging has emerged as a non-invasive method for assessing intracranial arteries. The reading and interpretation of wall imaging is subject to numerous artefacts despite optimised protocols and therefore to erroneous interpretations.
The wall imaging sequences were carried out according to the recommendations on a 3T MRI with the acquisition of 3D sequences in planes other than the axial plane to limit artefacts (coronal and sagittal respectively),but without a dual orthogonal plan (i.e sagittal and coronal for a same patient), and with an isotropic slice thickness of 0.8mm, above the 0,5mm or less isotropic required for quality imaging.(2)
Irregular velocity patterns, including disturbed or recirculating flow, can enhance incomplete signal suppression at the lumen's periphery, potentially simulating eccentric or concentric thickening of the vessel wall, which may therefore mimic atherosclerotic plaque or vasculitis (3).
Contrast-enhanced gadolinium magnetic resonance angiography reconstructions matched are mandatory to confirm real lumen patency without irregularity, enabling confirmation of the suspected wall thickening as artifactual, and this sequence is not included in the study protocol. There is only one 3D TOF (Time of Flight) vascular sequence in the protocol of this study, which is also prone to numerous artefacts and only have 59% positive predictive value to diagnose a 50-99% intracranial stenosis. TOF need another imaging method to confirm stenosis and is less accurate than contrast enhanced imaging in assessing luminal stenosis.(4)
In addition, there is no high-resolution 3D T2 wall imaging sequence to confirm the presence of intraluminal thickening, and also detect positive or negative remodeling pattern. The choice of the presence of a 2D sequence only in the plane of the middle cerebral artery demonstrates an incomplete exploration of the vascular tree.
The authors chose to carry out T1-weighted imaging of the wall (better contrast and better cancellation of the CSF signal), but it would have been interesting to see whether the results were also reproducible on PD (Proton Density)-weighted imaging (better theoretical resolution).
There is an absence of use of the preparatory sequence MSDE (Motion Sensitized Driven Equilibrium) consisting of three non-selective RF pulses (with angles of inclination of 90°-180°-90°) to suppress any vascular signal, and avoids interpreting residual venous slow flows as an pathological enhancement.(5,6)
It is surprising not to have a susceptibility weighted sequence (SWI or T2*) in the study protocol in the context of vasculitis to detect the presence of microbleeds. There is inflammatory response surrounding microhemorrhages, that may resemble an inflammatory process involving the vessel wall with surrounding enhancement and mimick perivascular inflammation, especially since the signal loss from the microbleed can resemble the flow-suppressed lumen on vessel wall imaging.(3)
Caution should be exercised when interpreting the enhancement of the V4 segments of the vertebral arteries, with the frequent presence of intradural vascular plexuses or vasa vasorum which increase with age, this can lead to concentric arterial wall thickening and enhancement that can mimic the appearance of vasculitis or atherosclerotic plaque. Although they are typically absent in young subjects.(7)
Atherosclerosis was solely defined as follows: eccentric vessel wall thickening in the orthogonal plane, with the maximal wall thickness exceeding twice the thinnest wall thickness on visual inspection.
This definition does not account for the full spectrum of imaging presentations of atherosclerotic lesions, particularly hemorrhagic plaques, which exhibit a spontaneous T1 hyperintensity within the vessel wall (observed in up to 20% of symptomatic cases).(8) The absence of a non-contrast 3D T1 vessel wall imaging sequence in the study protocol prevents the diagnosis of such lesions, potentially overlooking atherosclerotic involvement.
Moreover, the interpretation of vessel wall enhancement of this study is not reliable, as the true presence of vessel wall enhancement cannot be confirmed without a pre-contrast T1 sequence prior to gadolinium administration. Nothing guarantees the absence of spontaneous T1 hyperintensity in such conditions.
In addition, eccentric vessel wall thickening can also be found, though not exclusively, in other non-atherosclerotic pathologies such as Moyamoya disease(9), and concentric vessel wall thickening can also be seen in reversible cerebral vasoconstriction syndrome, even though the authors clearly state that they have excluded these patients.(10)
With all these different possible artefacts tending to create numerous false-positives, the results of wall imaging should be interpreted with caution, particularly when multiple vessels lesions are suspected.
For the mixed atherovasculitis subgroup there is a very large proportion of patients (n=8/26 ; 30%) whose main pathology is antiphospholipid syndrome (APS).
There are few studies in the literature on the appearance of intracranial APS vasculopathy on MRI. However, this pathology appears to have a variable presentation, with predominantly long stenoses (as illustrated in Figure 1I on the left M2 segment), in contrast to the shorter atherosclerotic stenoses. Vessel wall imaging reveals concentric or eccentric thickening with variable parietal or intraluminal enhancement (in cases of thrombosis)(11–13)
This variability in imaging appearance is related to the complex pathophysiology of APS vasculopathy. Endothelial cells can be stimulated, leading to the proliferation of vascular cells in the intima and media without the formation of an intraluminal thrombus. This non-thrombotic proliferative vasculopathy associated with APS may result in significant narrowing of the pulmonary, visceral, and peripheral arteries. Unlike an arterial thrombus in APS or an atherosclerotic plaque, which can cause sudden, short-segment stenosis or occlusion, APS may trigger widespread thickening of the vascular wall, leading to long-segment stenosis.
Even though it is known that atherosclerosis is observed more frequently in patients with primary antiphospholipid, (14) due to the complexity of the possible and interwoven pathophysiological mechanisms in APS vasculopathy, it is not possible to attribute arterial stenoses solely to atherosclerosis or to its combination with "vasculitis." It is conceivable that these arterial stenoses are exclusively linked to APS through non-thrombotic mechanisms of proliferative vasculopathy. Only a histopathological study of intracranial arteries would provide definitive clarification on these questions.
However, this study reminds us that inflammatory pathologies are closely linked to the accelerated development of atherosclerosis, and that atheroma and vasculitis may coexist with dramatic consequences in the form of frequent strokes. Vessel wall imaging is a highly promising tool for identifying the etiology of arterial lesions and thereby guiding therapeutic strategies.
A further study, with a more in-depth consideration of potential sources of artifacts and false or true positives, is necessary to confirm these findings.
1. Li S, Yu Q, Zhou Y, Ding M, Zhou H, Liu Y, et al. The Etiology of Intracranial Artery Stenosis in Autoimmune Rheumatic Diseases: An Observational High-Resolution MR Imaging Study. American Journal of Neuroradiology. 1 févr 2025;46(2):265‑71.
2. Mandell DM, Mossa-Basha M, Qiao Y, Hess CP, Hui F, Matouk C, et al. Intracranial Vessel Wall MRI: Principles and Expert Consensus Recommendations of the American Society of Neuroradiology. AJNR Am J Neuroradiol. févr 2017;38(2):218‑29.
3. Kang N, Qiao Y, Wasserman BA. Essentials for Interpreting Intracranial Vessel Wall MRI Results: State of the Art. Radiology. sept 2021;300(3):492‑505.
4. Feldmann E, Wilterdink JL, Kosinski A, Lynn M, Chimowitz MI, Sarafin J, et al. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial. Neurology. 12 juin 2007;68(24):2099‑106.
5. Sannananja B, Zhu C, Colip CG, Somasundaram A, Ibrahim M, Khrisat T, et al. Image-Quality Assessment of 3D Intracranial Vessel Wall MRI Using DANTE or DANTE-CAIPI for Blood Suppression and Imaging Acceleration. American Journal of Neuroradiology [Internet]. 26 mai 2022 [cité 19 févr 2025]; Disponible sur: https://www.ajnr.org/content/early/2022/05/26/ajnr.A7531
6. Kim DJ, Lee HJ, Baik J, Hwang MJ, Miyoshi M, Kang Y. Improved Blood Suppression of Motion-Sensitized Driven Equilibrium in High-Resolution Whole-Brain Vessel Wall Imaging: Comparison of Contrast-Enhanced 3D T1-Weighted FSE with Motion-Sensitized Driven Equilibrium and Delay Alternating with Nutation for Tailored Excitation. American Journal of Neuroradiology [Internet]. 20 oct 2022 [cité 19 févr 2025]; Disponible sur: https://www.ajnr.org/content/early/2022/10/20/ajnr.A7678
7. Harteveld AA, van der Kolk AG, van der Worp HB, Dieleman N, Siero JCW, Kuijf HJ, et al. High-resolution intracranial vessel wall MRI in an elderly asymptomatic population: comparison of 3T and 7T. Eur Radiol. 2017;27(4):1585‑95.
8. Xu WH, Li ML, Gao S, Ni J, Yao M, Zhou LX, et al. Middle cerebral artery intraplaque hemorrhage: prevalence and clinical relevance. Ann Neurol. févr 2012;71(2):195‑8.
9. Larson AS, Klaas JP, Johnson MP, Benson JC, Shlapak D, Lanzino G, et al. Vessel wall imaging features of Moyamoya disease in a North American population: patterns of negative remodelling, contrast enhancement, wall thickening, and stenosis. BMC Medical Imaging. 17 nov 2022;22(1):198.
10. Chen CY, Chen SP, Fuh JL, Lirng JF, Chang FC, Wang YF, et al. Vascular wall imaging in reversible cerebral vasoconstriction syndrome – a 3-T contrast-enhanced MRI study. J Headache Pain. 30 août 2018;19(1):74.
11. Yeo J, Hwang I, Sohn CH, Lee EE, Lee ST, Lee EB, et al. Proliferative Vasculopathy Associated With Antiphospholipid Antibodies in Patients With Neurological Symptoms. Front Med (Lausanne). 20 juin 2022;9:913203.
12. Benjamin LA, Lim E, Sokolska M, Markus J, Zaletel T, Aggarwal V, et al. Vessel wall magnetic resonance and arterial spin labelling imaging in the management of presumed inflammatory intracranial arterial vasculopathy. Brain Commun. 20 juin 2022;4(4):fcac157.
13. Provenzale JM, Barboriak DP, Allen NB, Ortel TL. Antiphospholipid antibodies: findings at arteriography. AJNR Am J Neuroradiol. avr 1998;19(4):611‑6.
14. Zhang G, Cai Q, Zhou H, He C, Chen Y, Zhang P, et al. OxLDL/β2GPI/anti-β2GPI Ab complex induces inflammatory activation via the TLR4/NF-κB pathway in HUVECs. Mol Med Rep. févr 2021;23(2):148.
I would like to thank Shun et al(1) for their very relevant work in assessing the added value of vessel wall imaging in auto-immune rheumatic diseases for the etiology of intracranial artery stenosis. High resolution wall imaging has emerged as a non-invasive method for assessing intracranial arteries. The reading and interpretation of wall imaging is subject to numerous artefacts despite optimised protocols and therefore to erroneous interpretations.
The wall imaging sequences were carried out according to the recommendations on a 3T MRI with the acquisition of 3D sequences in planes other than the axial plane to limit artefacts (coronal and sagittal respectively),but without a dual orthogonal plan (i.e sagittal and coronal for a same patient), and with an isotropic slice thickness of 0.8mm, above the 0,5mm or less isotropic required for quality imaging.(2)
Irregular velocity patterns, including disturbed or recirculating flow, can enhance incomplete signal suppression at the lumen's periphery, potentially simulating eccentric or concentric thickening of the vessel wall, which may therefore mimic atherosclerotic plaque or vasculitis (3).
Contrast-enhanced gadolinium magnetic resonance angiography reconstructions matched are mandatory to confirm real lumen patency without irregularity, enabling confirmation of the suspected wall thickening as artifactual, and this sequence is not included in the study protocol. There is only one 3D TOF (Time of Flight) vascular sequence in the protocol of this study, which is also prone to numerous artefacts and only have 59% positive predictive value to diagnose a 50-99% intracranial stenosis. TOF need another imaging method to confirm stenosis and is less accurate than contrast enhanced imaging in assessing luminal stenosis.(4)
In addition, there is no high-resolution 3D T2 wall imaging sequence to confirm the presence of intraluminal thickening, and also detect positive or negative remodeling pattern. The choice of the presence of a 2D sequence only in the plane of the middle cerebral artery demonstrates an incomplete exploration of the vascular tree.
The authors chose to carry out T1-weighted imaging of the wall (better contrast and better cancellation of the CSF signal), but it would have been interesting to see whether the results were also reproducible on PD (Proton Density)-weighted imaging (better theoretical resolution).
There is an absence of use of the preparatory sequence MSDE (Motion Sensitized Driven Equilibrium) consisting of three non-selective RF pulses (with angles of inclination of 90°-180°-90°) to suppress any vascular signal, and avoids interpreting residual venous slow flows as an pathological enhancement.(5,6)
It is surprising not to have a susceptibility weighted sequence (SWI or T2*) in the study protocol in the context of vasculitis to detect the presence of microbleeds. There is inflammatory response surrounding microhemorrhages, that may resemble an inflammatory process involving the vessel wall with surrounding enhancement and mimick perivascular inflammation, especially since the signal loss from the microbleed can resemble the flow-suppressed lumen on vessel wall imaging.(3)
Caution should be exercised when interpreting the enhancement of the V4 segments of the vertebral arteries, with the frequent presence of intradural vascular plexuses or vasa vasorum which increase with age, this can lead to concentric arterial wall thickening and enhancement that can mimic the appearance of vasculitis or atherosclerotic plaque. Although they are typically absent in young subjects.(7)
Atherosclerosis was solely defined as follows: eccentric vessel wall thickening in the orthogonal plane, with the maximal wall thickness exceeding twice the thinnest wall thickness on visual inspection.
This definition does not account for the full spectrum of imaging presentations of atherosclerotic lesions, particularly hemorrhagic plaques, which exhibit a spontaneous T1 hyperintensity within the vessel wall (observed in up to 20% of symptomatic cases).(8) The absence of a non-contrast 3D T1 vessel wall imaging sequence in the study protocol prevents the diagnosis of such lesions, potentially overlooking atherosclerotic involvement.
Moreover, the interpretation of vessel wall enhancement of this study is not reliable, as the true presence of vessel wall enhancement cannot be confirmed without a pre-contrast T1 sequence prior to gadolinium administration. Nothing guarantees the absence of spontaneous T1 hyperintensity in such conditions.
In addition, eccentric vessel wall thickening can also be found, though not exclusively, in other non-atherosclerotic pathologies such as Moyamoya disease(9), and concentric vessel wall thickening can also be seen in reversible cerebral vasoconstriction syndrome, even though the authors clearly state that they have excluded these patients.(10)
With all these different possible artefacts tending to create numerous false-positives, the results of wall imaging should be interpreted with caution, particularly when multiple vessels lesions are suspected.
For the mixed atherovasculitis subgroup there is a very large proportion of patients (n=8/26 ; 30%) whose main pathology is antiphospholipid syndrome (APS).
There are few studies in the literature on the appearance of intracranial APS vasculopathy on MRI. However, this pathology appears to have a variable presentation, with predominantly long stenoses (as illustrated in Figure 1I on the left M2 segment), in contrast to the shorter atherosclerotic stenoses. Vessel wall imaging reveals concentric or eccentric thickening with variable parietal or intraluminal enhancement (in cases of thrombosis)(11–13)
This variability in imaging appearance is related to the complex pathophysiology of APS vasculopathy. Endothelial cells can be stimulated, leading to the proliferation of vascular cells in the intima and media without the formation of an intraluminal thrombus. This non-thrombotic proliferative vasculopathy associated with APS may result in significant narrowing of the pulmonary, visceral, and peripheral arteries. Unlike an arterial thrombus in APS or an atherosclerotic plaque, which can cause sudden, short-segment stenosis or occlusion, APS may trigger widespread thickening of the vascular wall, leading to long-segment stenosis.
Even though it is known that atherosclerosis is observed more frequently in patients with primary antiphospholipid, (14) due to the complexity of the possible and interwoven pathophysiological mechanisms in APS vasculopathy, it is not possible to attribute arterial stenoses solely to atherosclerosis or to its combination with "vasculitis." It is conceivable that these arterial stenoses are exclusively linked to APS through non-thrombotic mechanisms of proliferative vasculopathy. Only a histopathological study of intracranial arteries would provide definitive clarification on these questions.
However, this study reminds us that inflammatory pathologies are closely linked to the accelerated development of atherosclerosis, and that atheroma and vasculitis may coexist with dramatic consequences in the form of frequent strokes. Vessel wall imaging is a highly promising tool for identifying the etiology of arterial lesions and thereby guiding therapeutic strategies.
A further study, with a more in-depth consideration of potential sources of artifacts and false or true positives, is necessary to confirm these findings.
1. Li S, Yu Q, Zhou Y, Ding M, Zhou H, Liu Y, et al. The Etiology of Intracranial Artery Stenosis in Autoimmune Rheumatic Diseases: An Observational High-Resolution MR Imaging Study. American Journal of Neuroradiology. 1 févr 2025;46(2):265‑71.
2. Mandell DM, Mossa-Basha M, Qiao Y, Hess CP, Hui F, Matouk C, et al. Intracranial Vessel Wall MRI: Principles and Expert Consensus Recommendations of the American Society of Neuroradiology. AJNR Am J Neuroradiol. févr 2017;38(2):218‑29.
3. Kang N, Qiao Y, Wasserman BA. Essentials for Interpreting Intracranial Vessel Wall MRI Results: State of the Art. Radiology. sept 2021;300(3):492‑505.
4. Feldmann E, Wilterdink JL, Kosinski A, Lynn M, Chimowitz MI, Sarafin J, et al. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial. Neurology. 12 juin 2007;68(24):2099‑106.
5. Sannananja B, Zhu C, Colip CG, Somasundaram A, Ibrahim M, Khrisat T, et al. Image-Quality Assessment of 3D Intracranial Vessel Wall MRI Using DANTE or DANTE-CAIPI for Blood Suppression and Imaging Acceleration. American Journal of Neuroradiology [Internet]. 26 mai 2022 [cité 19 févr 2025]; Disponible sur: https://www.ajnr.org/content/early/2022/05/26/ajnr.A7531
6. Kim DJ, Lee HJ, Baik J, Hwang MJ, Miyoshi M, Kang Y. Improved Blood Suppression of Motion-Sensitized Driven Equilibrium in High-Resolution Whole-Brain Vessel Wall Imaging: Comparison of Contrast-Enhanced 3D T1-Weighted FSE with Motion-Sensitized Driven Equilibrium and Delay Alternating with Nutation for Tailored Excitation. American Journal of Neuroradiology [Internet]. 20 oct 2022 [cité 19 févr 2025]; Disponible sur: https://www.ajnr.org/content/early/2022/10/20/ajnr.A7678
7. Harteveld AA, van der Kolk AG, van der Worp HB, Dieleman N, Siero JCW, Kuijf HJ, et al. High-resolution intracranial vessel wall MRI in an elderly asymptomatic population: comparison of 3T and 7T. Eur Radiol. 2017;27(4):1585‑95.
8. Xu WH, Li ML, Gao S, Ni J, Yao M, Zhou LX, et al. Middle cerebral artery intraplaque hemorrhage: prevalence and clinical relevance. Ann Neurol. févr 2012;71(2):195‑8.
9. Larson AS, Klaas JP, Johnson MP, Benson JC, Shlapak D, Lanzino G, et al. Vessel wall imaging features of Moyamoya disease in a North American population: patterns of negative remodelling, contrast enhancement, wall thickening, and stenosis. BMC Medical Imaging. 17 nov 2022;22(1):198.
10. Chen CY, Chen SP, Fuh JL, Lirng JF, Chang FC, Wang YF, et al. Vascular wall imaging in reversible cerebral vasoconstriction syndrome – a 3-T contrast-enhanced MRI study. J Headache Pain. 30 août 2018;19(1):74.
11. Yeo J, Hwang I, Sohn CH, Lee EE, Lee ST, Lee EB, et al. Proliferative Vasculopathy Associated With Antiphospholipid Antibodies in Patients With Neurological Symptoms. Front Med (Lausanne). 20 juin 2022;9:913203.
12. Benjamin LA, Lim E, Sokolska M, Markus J, Zaletel T, Aggarwal V, et al. Vessel wall magnetic resonance and arterial spin labelling imaging in the management of presumed inflammatory intracranial arterial vasculopathy. Brain Commun. 20 juin 2022;4(4):fcac157.
13. Provenzale JM, Barboriak DP, Allen NB, Ortel TL. Antiphospholipid antibodies: findings at arteriography. AJNR Am J Neuroradiol. avr 1998;19(4):611‑6.
14. Zhang G, Cai Q, Zhou H, He C, Chen Y, Zhang P, et al. OxLDL/β2GPI/anti-β2GPI Ab complex induces inflammatory activation via the TLR4/NF-κB pathway in HUVECs. Mol Med Rep. févr 2021;23(2):148.