Various imaging modalities, including color duplex ultrasonography, CT angiography, magnetic resonance angiography, and PET, are emerging as important aids to the diagnosis, staging, evaluation of disease activity and response to treatment in systemic vasculitis. Although large-vessel vasculitis is the main target of imaging, refinement and increasing accuracy of imaging modalities are also providing useful information in the evaluation of medium-vessel and small-vessel vasculitis.
Key points
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Imaging is emerging as an invaluable aid to the diagnosis of systemic vasculitis.
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Existing imaging modalities have advantages and disadvantages as well as preferred indications for different purposes.
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Although large-vessel vasculitides (LVVs) are the most easily detected by imaging, preliminary data indicate that PET may be useful in detecting the extent of organ involvement in medium-sized vasculitis and small-vessel vasculitis.
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Imaging has contributed to determine the pathologic substrate underlying polymyalgia rheumatic (PMR) and its relationship to giant cell arteritis (GCA) or other rheumatic diseases.
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Imaging may have a role in the assessment of disease activity and response to treatment but standardization and validation are needed before its use as an outcome measure.
Introduction
Systemic vasculitides, characterized by inflammation of blood vessels, preferentially target vessels of different sizes. This characteristic has been used for categorization and is clinically helpful because LVV, medium-vessel vasculitis, or small-vessel vasculitis benefits from different diagnostic approaches.
The segmental nature of vascular inflammatory lesions, variability in tissue targeting, inaccessibility of large vessels, and risk associated with visceral biopsies have promoted development of imaging as a surrogate or complement to histopathologic demonstration of vascular inflammation. Imaging is becoming an important tool in the global assessment of patients with LVV, in the detection of vascular structural abnormalities or target organ damage in patients with medium-sized vessel vasculitis, and is emerging as a useful tool to determine the extent of organ involvement in small-vessel vasculitis. In addition to providing a surrogate of histopathologic confirmation in certain settings, imaging has the great advantage of exploring a wide range of vascular territories as opposed to the limited sampling of a tissue biopsy and offers the possibility of nonaggressive sequential assessments.
The most extensively used imaging modalities include color duplex ultrasonography (CDUS), CT angiography (CTA), magnetic resonance angiography (MRA), and PET (usually combined with CT). Except for the classic detection of stenoses or microaneurysms in medium-sized vessel vasculitis, conventional angiography has become a therapeutic procedure for endovascular intervention rather than a diagnostic method. Advantages and disadvantages of the available techniques are summarized in Table 1 .
| Modality | Features | Advantages | Disadvantages |
|---|---|---|---|
| CTA |
|
|
|
| MRI/MRA |
|
|
|
| PET/PET-CT | 18 FDG uptake reflecting increased metabolism |
|
|
| CDUS |
|
|
|
| Angiography | Lumen patency assessment |
|
|
Introduction
Systemic vasculitides, characterized by inflammation of blood vessels, preferentially target vessels of different sizes. This characteristic has been used for categorization and is clinically helpful because LVV, medium-vessel vasculitis, or small-vessel vasculitis benefits from different diagnostic approaches.
The segmental nature of vascular inflammatory lesions, variability in tissue targeting, inaccessibility of large vessels, and risk associated with visceral biopsies have promoted development of imaging as a surrogate or complement to histopathologic demonstration of vascular inflammation. Imaging is becoming an important tool in the global assessment of patients with LVV, in the detection of vascular structural abnormalities or target organ damage in patients with medium-sized vessel vasculitis, and is emerging as a useful tool to determine the extent of organ involvement in small-vessel vasculitis. In addition to providing a surrogate of histopathologic confirmation in certain settings, imaging has the great advantage of exploring a wide range of vascular territories as opposed to the limited sampling of a tissue biopsy and offers the possibility of nonaggressive sequential assessments.
The most extensively used imaging modalities include color duplex ultrasonography (CDUS), CT angiography (CTA), magnetic resonance angiography (MRA), and PET (usually combined with CT). Except for the classic detection of stenoses or microaneurysms in medium-sized vessel vasculitis, conventional angiography has become a therapeutic procedure for endovascular intervention rather than a diagnostic method. Advantages and disadvantages of the available techniques are summarized in Table 1 .
| Modality | Features | Advantages | Disadvantages |
|---|---|---|---|
| CTA |
|
|
|
| MRI/MRA |
|
|
|
| PET/PET-CT | 18 FDG uptake reflecting increased metabolism |
|
|
| CDUS |
|
|
|
| Angiography | Lumen patency assessment |
|
|
Large-vessel vasculitis
Imaging may provide valuable information on different aspects relevant to the management of patients with LVV ( Box 1 ). The most widely explored is the contribution of imaging to diagnosis. Imaging detects vascular inflammation by revealing radiotracer uptake or thickening of the vessel wall in involved arteries. It is also useful in assessing disease extent by exploring multiple vascular beds and, distribution may, in turn, be useful for differential diagnosis (discussed later). Moreover, imaging may have potential to evaluate disease activity and treatment efficacy and may become a valuable outcome measure. Imaging is also crucial in detecting vascular damage and structural abnormalities, including dilatation and stenoses. All these different aspects are the focus of this review. Disappointingly, except for CDUS, most published studies consist of case reports, small case series, and post hoc or retrospective assessments, including heterogeneous patients in different disease activity states. Prospective, controlled studies using MRA, CTA, or PET are still scarce and different concepts, such as diagnosis, extent, evaluation of disease activity, response to treatment, and damage/remodeling are frequently mixed under the concept of “involvement” and have not been clearly delineated or specifically addressed.
Diagnosis
Demonstration of temporal artery involvement in GCA
CDUS
MRI
Evidence of LVV in both GCA and TAK
CDUS supra-aortic branches and extremity arteries
PET aorta and major tributaries
MRA/CTA aorta and major branches; extremity arteries
Evaluation of disease extent a
CDUS supra-aortic branches and extremity arteries
PET aorta and major branches; target organ involvement in small-vessel vasculitis
MRA/CTA aorta and tributaries; extremity arteries
MRA/CTA/conventional angiography of coronary or intracranial arteries in selected patients
Evaluation of response to treatment (outcome measure) b
CDUS
PET
CTA/MRA
CEUS
Detection of structural damage
Aortic/aortic branch dilatation or aneurysm (CT/MRI)
Vascular stenoses (CTA, MRA, CDUS, conventional angiography)
Ischemic infarcts (CT/CTA, MRI/MRA)
Therapeutic intervention
Conventional angiography (angioplasty, stenting, endovascular graft, embolization)
a Pattern of involvement may be useful in differentiating from other diseases (ie, periaortitis, isolated aortitis, vascular involvement by IgG4-related disease).
b Appealing role but no solid/definitive data are available.
Imaging for Large-vessel Vasculitis Diagnosis
Imaging in its evolving modalities has traditionally been the cornerstone of diagnosis of Takayasu arteritis (TAK) due to the inaccessibility of the primarily involved vessels to biopsy sampling. In the past decade, the relevance of imaging in the diagnosis of GCA has been exponentially appreciated. GCA diagnosis has classically relied on examination of temporal artery biopsies (TABs) or, based on the common difficulties in obtaining a timely and optimal biopsy, on clinical assessment with all its potential pitfalls and dependence on the experience of the diagnosing physician. Imaging has definitely expanded the diagnostic armamentarium of GCA beyond subjective clinical assessment.
Among imaging techniques, CDUS of the temporal artery has an outstanding sensitivity and specificity for GCA diagnosis, especially when hypoechoic edematous wall swelling (halo sign) is detected ( Fig. 1 ). A remarkable number of articles, systematic reviews, and meta-analyses support the usefulness of CDUS for the diagnosis of GCA and it is widely used in clinical practice. An advantage of CDUS compared with TAB is the potential assessment of longer artery segments or additional vascular beds because GCA may not invariably involve the superficial temporal artery. CDUS has demonstrated that occipital arteries may be involved in approximately 66% to 69% of patients. Moreover, involvement of the subclavian, proximal brachial, and axillary arteries as well as distal extremity arteries, such as ulnar or popliteal arteries, can also be detected by CDUS. Exploring the axillary and common carotid arteries in addition to the temporal arteries may improve the diagnostic performance of CDUS, underlying the advantage of imaging in assessing multiple vascular territories. It has been hypothesized that CDUS-guided selection of the temporal artery segment to be excised may increase the sensitivity of the TAB. A recent prospective, randomized study found, however, that CDUS-guided TAB did not result in higher rate of positive results than TAB guided by physical examination.
CDUS requires specific training and interobserver variability may be wide. With respect to TAB, CDUS may fail to detect mild histopathologic abnormalities, such as inflammation limited to adventitia or periadventitial small vessels. In a recent study, the frequency of detection of the halo sign by CDUS was significantly lower in patients with incomplete histopathologic findings compared with those with classic transmural inflammation. An international, multicenter study aimed at prospectively comparing the diagnostic performance of CDUS versus TAB in a large cohort of patients is ongoing ( NCT00974883 ).
Microbubble contrast-enhanced ultrasound (CEUS) is a novel improved method that detects vascular neovascularization and is increasingly used for vascular imaging in the context of atherosclerosis. Angiogenesis is prominent in systemic vasculitis and occurs within the vessel walls of involved arteries in LVV. Along with an inflammation-driven increase in vascular permeability, angiogenesis leads to intramural microbubble accumulation. A small prospective study comparing CDUS with CEUS for the assessment of carotid artery inflammation in LVV disclosed that CEUS provided better image quality, definition of the lumen-to-vascular wall border, and detection of vessel wall neovascularization.
High-resolution MRI has a sensitivity and specificity similar to CDUS in detecting temporal artery involvement in GCA, although its routine use for this purpose is not widely feasible. A multicenter prospective study showed that high-resolution MRI has a sensitivity of 78.4% and a specificity of 90.4% in detecting temporal artery involvement in patients with clinical diagnosis of GCA and a sensitivity of 88.7% and specificity of 75% using biopsy-proved disease as a reference. In addition, MRI may detect additional findings, such as deep temporal artery involvement and temporal muscle edema, in 20% to 40% of patients.
In recent years, the diagnostic usefulness of detecting large-vessel inflammation (aorta and its major tributaries) in GCA by imaging has been increasingly appreciated. CTA, MRA, and PET are widely used for this purpose. CTA reveals concentric mural thickening and a double-ring enhancement after administration of contrast in the venous phase ( Fig. 2 ). Mural calcifications are clearly detected by CT and this finding allows distinction between focal thickening associated with atheroma and concentric thickening suggesting vasculitis. CTA is useful for large-vessel imaging due to its excellent spatial resolution and short acquisition time. Although radiation is of concern for serial explorations, new low-dose CT techniques and reconstruction systems have achieved a remarkable reduction in radiation exposure.
