3D Whole Brain Vessel Wall Imaging of Primary Angiitis of the Central Nervous System: 5 Cases and Literature Review

Primary angiitis of the central nervous system is an uncommon single-organ vasculitis that is still poorly understood, and its diagnosis can be quite challenging. Traditional vascular imaging techniques could only show the abnormality of vessel lumen, while primary angiitis of the central nervous system as well as atherosclerosis or other mimics could show similar patterns, like tapering of the vessel lumen or multiple stenosis. Vessel wall magnetic resonance imaging can directly visualize the abnormality of the vessel wall, therefore has become a valuable approach for vasculopathy evaluation. However, 2D vessel wall magnetic resonance imaging can only be restricted to one fixed angle for one scanning process, while vasculitis tends to involve multiple vessels. With the development of 3D isotropic vessel wall imaging sequence, it can achieve a thorough view of the whole brain vasculature in shorter time and apply reconstruction in any angle. Reasonably, 3D isotropic vessel wall imaging could help with the diagnosis, evaluation and follow-up of primary angiitis of the central nervous system more effectively.


KEYWORDS
vessel wall imaging, primary angiitis of the central nervous system Background Primary angiitis of the central nervous system is an uncommon single-organ vasculitis that is still poorly understood, and its diagnosis can be quite challenging. Traditional vascular imaging techniques could only show the abnormality of vessel lumen, while primary angiitis of the central nervous system as well as atherosclerosis or other mimics could show similar patterns, like tapering of the vessel lumen or multiple stenosis. Vessel wall magnetic resonance imaging can directly visualize the abnormality of the vessel wall, therefore has become a valuable approach for vasculopathy evaluation. However, 2D vessel wall magnetic resonance imaging can only be restricted to one fixed angle for one scanning process, while vasculitis tends to involve multiple vessels. With the development of 3D isotropic vessel wall imaging sequence, it can achieve a thorough view of the whole brain vasculature in shorter time and apply reconstruction in any angle. Reasonably, 3D isotropic vessel wall imaging could help with the diagnosis, evaluation and follow-up of primary angiitis of the central nervous system more effectively.

Case presentation
We present five cases of primary angiitis of the central nervous system that underwent 3D isotropic vessel wall imaging, along with follow-up. The diagnosis of primary angiitis of the central nervous system was made by classic diagnosis criteria. The youngest patient was 21 years old, while the oldest one was 49 years old. As for disease onset, one patient presented with headache, while other four patients presented with ischemic stroke. Both anterior circulation and posterior circulation of the five patients were involved, regardless of the responsible vessel. They were given steroids, immunosuppressor or parahormone for management. On follow-up vessel imaging, one patient displayed gradual vessel occlusion in 12 months, one patient showed partial resolution, other three patients presented with vasculopathy persistence.

Conclusions
3D isotropic vessel wall imaging could evaluate the specific responsible vessel as well as the whole brain vasculature in one-time scan, providing detailed information in detection, diagnosis, evaluation and follow-up. Moreover, primary angiitis of the central nervous system tend to be multi-vessel involving, so the 3D isotropic vessel wall imaging could be more applicable.  (4,5). However, the scanning process of vasculopathy by 2D VW-MRI can only be restricted to one fixed angle for one time scanning process, while vasculitis tends to involve multiple vessels. Also, intracranial vessels can be quite tortuous, so it is difficult to interpret the images precisely through one fixed plane (6). Besides, some lesions of the vasculature may be asymptomatic or non-stenotic on TOF-MRA, while 2D VW-MRI sequences are generally applied on stenotic segments, so the non-stenotic or asymptomatic lesions might be overlooked. 3D isotropic VW-MRI can reduce total scan time, providing more flexibility in radiograph reading, supporting image reconstruction from all angles. Furthermore, it can achieve a whole view of the head and neck vasculature in about 6 minutes, providing thorough information for the whole brain vasculature evaluation. Since PACNS tend to be multi-vessel involving, 3D isotropic VW-MRI could be more appropriate.
In this article, we present 5 cases that were ultimately diagnosed of PACNS, with particular imaging characteristics on 3D isotropic VW-MRI and follow-up, which could provide some information on the application of 3D isotropic VW-MRI in PACNS.

Case Presentation
We retrospectively reviewed the imaging database of 3D cerebral artery (MCA) territory, whereas magnetic resonance angiography (MRA) showed diffuse stenosis of the right internal carotid artery (ICA) and the right MCA ( Fig 1A). Laboratory tests for rheumatologic disorders, autoimmune diseases, and infectious causes of vasculopathy were all negative. 3D isotropic VW-MRI showed uniform thickening of the right ICA vessel wall with contrast enhancement (Fig 1B). Intravenous dexamethasone 15 mg was prescribed for 9 days. After discharge, steroid therapy was adjusted to dexamethasone 60 mg orally and then reduced to 10 mg per 14 days.
The patient was followed up at 2, 3, 6, and 12 months, and no acute ischemic infarction was noted.
For the 3-month imaging follow-up, the stenosis of the right ICA had not reverted (Fig 1D), while the enhancement intensity declined ( Figure 1E). But it was worth noting that the vessel wall of the left vertebral artery had been thickening ( Fig 1F) compared with baseline imaging (Fig 1C), and occluded on 6 months ( pyramidal sign was identified. The patient denied any traditional cerebrovascular risk factors other than smoking, with no history of drug abuse. DWI confirmed acute ischemic infarction in the right centrum semiovale. MRA revealed occlusion of the right ICA, and the right MCA was not visualized (Add Fig 1A). Laboratory tests for rheumatologic disorders, autoimmune diseases, and infectious causes of vasculopathy were all negative. 3D isotropic VW-MRI showed uniform thickening of the vessel wall of the right ICA with contrast enhancement (Add Fig 1B-E). The patient was ultimately diagnosed of PACNS after thorough evaluation and was prescribed steroids for management. On 3 months, he still reported paroxysmal headache but did not complete a follow-up in neuroimaging.  Fig 3B). MRA demonstrated severe stenosis or occlusion of the bilateral ICA (Add Fig 3A). He was given aspirin and clopidogrel for management. Three months later, he returned to the clinic with defective vision. Neurologic examination revealed right-sided sensory loss, homonymous hemianopia, and difficulties in naming and expression and severe memory deficits. DWI showed acute infarction in the left posterior cerebral artery territory (Add Fig 3C). 3D isotropic VW-MRI showed vessel wall thickening of the right ICA with uniform enhancement (Add Fig 3D, E). Further laboratory parameters for vasculitis all remained within normal range. The patient was ultimately diagnosed as having PACNS. Experimental treatment using methylprednisolone was performed (1,000 mg/d, halved every 3 days). At follow-up almost 3 month later, 3D isotropic VW-MRI showed resolution of stenosis (Add Fig 3F, G).

Discussion And Conclusions
PACNS is an uncommon single-organ vasculitis that is still poorly understood (9)(10)(11). PACNS could lead to various neurological manifestations, including headache, altered cognition, focal weakness, and Nevertheless, diagnosing PACNS can be quite challenging because of its diverse clinical features and lack of crucial laboratory tests. Most of the mimicking conditions would not benefit from steroids and immunosuppressive therapy, so the accurate diagnosis is very important. Brain biopsy is still the gold standard and should be performed whenever possible. But due to the invasive nature of biopsy, it has its limits, especially for intracranial vessels (13).  (17)(18)(19)(20). Furthermore, in order to precisely interpret VW-MRI images, the images need to be analyzed in at least both long-axis and short-axis plane. But for 2D VW-MRI sequences, they can only be restricted to one fixed angle for one time scanning process(Add Fig 4D-F). Since the intracranial vessels can be oblique, curved, and tortuous, 2D sequences could lead to partial volume averaging effects and confound the vasculopathies (6,20). Since the 3D VW-MRI sequences we applied are isotropic, they can be reconstructed in any angle. Additionally, 3D isotropic VW-MRI sequences with a big field of view including both the complete brain vasculature as well as the cervical arteries can supply images more efficiently, with relatively less artefacts, in relatively less time, since they are more stable against laminar flow and other artifacts (21)(22)(23)  disease onset, while saw gradual occlusion in 12 months. (Fig 1, Tab 2). The findings in our study were consistent with previous researches, reminding us of the stubborn and aggressive nature of PACNS, as well as the importance of whole brain and neck vasculature evaluation. Our case series had several deficiencies, including the absence of brain biopsy evidence and incomplete imaging follow-up. But we do explore the utility of 3D isotropic VW-MRI in PACNS.
We assert that 3D isotropic VW-MRI can evaluate the specific vasculopathy as well as the whole brain vasculature more effectively. 3D isotropic vessel wall imaging could evaluate the specific responsible vessel as well as the whole brain vasculature in one-time scan, providing detailed information in detection, diagnosis, evaluation and follow-up. Moreover, primary angiitis of the central nervous system tend to be multi-vessel involving, so the 3D isotropic vessel wall imaging could be more applicable. Thus far, the application of imaging in PACNS was qualitative. In the future, as the improvement of 7 Tesla scanning techniques, VW-MRI may achieve quantification assessment of vasculitis and provide more utility for PACNS (33).

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