Practice Essentials
Takayasu arteritis (TAK) is a granulomatous vasculitis of unknown etiology that commonly affects the thoracic aorta and its branches, the pulmonary arteries, and the coronary arteries. It causes intimal fibroproliferation, which ultimately leads to segmental stenosis, occlusion, dilatation, and aneurysmal formation in these vessels. In North America, TAK has an incidence of 2.6 per million population. Ninety percent of patients with TAK are younger than 30 years. Women younger than 40 years are mostly affected. It occurs for the first time in childhood in about 30% of affected individuals. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13]
Imaging is considered the cornerstone of the diagnosis of TAK. Historically, angiography has been the criterion-standard imaging tool for diagnosis and evaluation. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) have become equally valuable tools. Their large fields of view, as well as the fact that they are noninvasive, make them far more attractive as diagnostic tools. [14, 15, 16]
CTA,MRA, or color Doppler ultrasound (CDUS) enables anatomic characterization of stenosis, dilatation, and vessel wall characteristics. Vascular wall uptake of 18-fluorodeoxyglucose (FDG) or other ligands using positron emission tomography computed CT(PET-CT) helps assess metabolic activity, which reflects disease activity well in a subset of TAK patients with normal acute-phase reactants. Angiographic scoring systems have been developed to quantitate the extent of vascular involvement in TAK. The increasing resolution of multidetector-row CT arrays has increased its diagnostic value. The soft tissue differentiation possible with MR techniques is valuable in distinguishing active from quiescent forms of TAK. [12, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25]
Although radiography is not a primary tool for diagnosis, radiographic manifestations have been historically described in patients with TAK. Loss of sharp definition and a wavy or scalloped appearance of the descending thoracic aorta have been described. [26] Linear calcifications tend to be present in the aortic arch (porcelain aorta) and in the descending thoracic aorta in chronic disease, sparing the ascending aorta. [27] Cardiomegaly, decreased pulmonary vessels, and rib notching can also be found. [26]
Karapolat and colleagues investigated F-18 FDG PET-CT scanning to assess disease activity in Takayasu arteritis and concluded that their study findings were consistent with clinical disease status. [28] Intense linear uptake of FDG is characteristic of active vasculitis. [29] This modality depicted positive findings in all patients with active disease in a retrospective analysis of patients with and without immunosuppression. [30, 31, 32]
Thallium-201 (201Tl) myocardial scintigraphy with dipyridamole (DPM) as a vasodilator agent has been utilized to identify patients with TAK who have asymptomatic myocardial involvement. [33]
Mavrogeni and colleagues suggested a practical approach to diagnosis of TAK and selection of imaging methods, as follows [29] :
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CT and MRI for luminography are less invasive than angiography and depict similar results.
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MRI should be used if possible over CT because of lack of radiation.
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The heart should be evaluated; MRI is superior.
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Ultrasound is excellent for evaluating extracranial carotid arteries.
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PET should be used if the main complaint is fever of unknown origin.
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PET/MRI should be selected over PET/CT or PET.
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Imaging findings should be correlated with clinical and laboratory findings.
(See the image of Takayasu arteritis below.)
Takayasu arteritis. A 48-year-old woman with Takayasu disease. Note the narrowing of the origin of the right subclavian artery and a narrowed small vessel with subsequent aneurysmal dilatation on the right side.
Ultrasonography
B-mode ultrasonography may depict homogeneous circumferential thickening of affected vessels, characterized by diffuse hypoechoic or isoechoic thickening of the affected wall on longitudinal scanning, classically described as the “macaroni sign,” which may represent edema, increased vascularity, or both. [29] B-mode morphologic study has further been utilized to monitor the progression of disease. In a follow-up study of 20 patients, [34] wall thickness and outer diameter of the carotid artery were increased in patients with disease relapse and were decreased in patients whose disease remained in remission. [35] Vascular stenosis, occlusions, and dilatation with increased flow velocity beyond the stenotic lesions are common findings on spectral Doppler ultrasound. [36] Dissections of the aorta, celiac artery, subclavian artery, vertebral artery, brachial artery, and femoral artery have been described. [37] Collateral formation of occluded carotid arteries frequently occurs and has incidentally suggested the diagnosis of Takayasu arteritis. [38]
A scoring system that correlates color Doppler ultrasound with clinical activity has been described, with statistically significant results in a study of 19 patients. A correlation was also found with angiographic findings at selected arterial sites. [39]
Contrast-enhanced ultrasound (CEUS) has permitted identification of flow within the thickened arterial wall, which corresponds to neovessels on the adventitial side during the initial inflammatory phase. [40, 41] In a study of 31 patients with large vessel vasculitis that compared CEUS vascularization grade with grade of vascular inflammation on FDG/PET as the gold standard, carotid CEUS showed 100% sensitivity and 92% specificity in detecting active vascular disease. [42]
CEUS has also been used to monitor response to immunosuppressive treatment. [43, 44]
Computed Tomography
In early disease, contrast CT demonstrates mural thickening, with intramural calcifications identified as the disease progresses. [18]
On CT angiography (CTA), precontrast scans show high attenuation of the aortic wall. The arterial phase reveals luminal changes such as stenosis, and the venous phase shows a double-ring pattern of the aortic wall. [45] Cardiac CTA has also detected silent coronary involvement characterized by nonostial stenosis, ostial stenosis, and coronary aneurysms. [46]
The CT differential diagnosis includes giant cell arteritis, polyarteritis nodosa, and atherosclerosis. [45]
The utility of this noninvasive technique is particularly high in pediatric patients, for whom complications of angiography are potentially worse than for adults. [47, 48]
One disadvantage of CT, as compared to conventional angiography, is that pressure differentials cannot be measured across lesions for which imaging findings regarding hemodynamic significance are inconclusive.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is one of the methods used most often to evaluate Takayasu arteritis. [49] It offers reproducibility and excellent luminography and lacks radiation. The utility of this noninvasive technique is particularly high in pediatric patients, for whom biological costs and complications of angiography are potentially greater than for adults. [50, 51, 52, 53, 54]
In cases of TAK, gadolinium-enhanced magnetic resonance angiography (MRA) may demonstrate concentric or crescent-like thickening of the arterial wall. [47] Inversion recovery–prepared echo-gradient pulse sequences with fat suppression depict indistinct outlines. Delayed hyperenhancement is seen in inflamed aortic arterial walls on delayed contrast-enhanced MRI. [55] Mural thrombi can be detected more easily on MRI than on conventional angiography. [56]
Zhang et al studied 52 consecutive TAK patients using a contrast-enhanced MRA sequence and determined that MRI enabled the comprehensive assessment of aortic wall morphology and functional markers for TAK disease activity. The most accurate indicator of TAK activity was aortic maximal wall thickness. Early phase was found to be superior to the delay phase for aortic wall enhancement analysis to assess TAK activity. [50]
In another study by Zhang et al, MRI-derived feature tracking (CMR-FT) was used to identify cardiac damage in TA patients. The authors found that global longitudinal strain (GLS) was significantly worse in TKA patients than in controls and that TA patients who received late gadolinium enhancement had significantly poorer GLS. In addition, patients with reduced LVEF had significantly greater cardiac dysfunction than those with preserved LVEF. [51]
Using CMR-FT, Guo et al found that patients with TAK and preserved left ventricular ejection fraction (pLVEF) had a decline in baseline global longitudinal peak strain (GLS) and circumferential peak strain versus controls. In addition, patients with pulmonary hypertension (PH) or myocardial late gadolinium enhancement (LGE) displayed a greater reduction in strain than those without PH or LGE. [52]
Assessment of disease activity is one of the major challenges for physicians. The soft tissue differentiation obtained with MR techniques may help distinguish the active or acute phase from the chronic phase of the disease. This capability may be important in the timing of catheter-based or other interventions.
Discerning between active disease and inactive disease with fibrosis has been a matter of extensive study, as the 2 entities have similar characteristics on contrast MRI. Contrast agents that compartmentalize to the intravascular space, such as gadofosveset trisodium, may be the answer to this problem. Significant enhancement of the arterial wall was identified in active disease, whereas no such enhancement was detected in fibrotic tissue. [57]
Cine MRI is fundamental in detecting cardiovascular and hemodynamic changes in patients with associated aortic regurgitation. [36]
Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD).
Limitations include the possibility of misdiagnosing stenosis as occlusions in vascular branch points, as well as the inability to identify and characterize calcifications. [36]
Angiography
Angiography has been considered the gold standard for diagnosis of Takayasu arteritis. [23] However, because of its invasiveness, angiography is not the first-line study in most patients, particularly in pediatric patients. Gadolinium-enhanced MRA findings may be diagnostic or may be strongly suggestive of the disease (see the images below). [58]
Takayasu arteritis. A 48-year-old woman with Takayasu disease. Note the narrowing of the origin of the right subclavian artery and a narrowed small vessel with subsequent aneurysmal dilatation on the right side.
Takayasu arteritis. Characteristic long, tapered, narrowing of the distal aorta and iliac vessels.
Takayasu arteritis. Narrowing of the proximal descending aorta and right brachiocephalic artery.
A new angiographic classification has been proposed, [59] which divides the disease into 5 types according to the vessels involved:
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Type I involves only the branches of the aortic arch.
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Type IIa involves the ascending aorta, the aortic arch, and its branches; type IIb involves type IIa vessels plus the descending aorta.
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Type III involves the descending aorta, the abdominal aorta, and/or the renal arteries.
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Type IV involves the abdominal aorta and/or the renal arteries.
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Type V involves type IIB and type IV combined.
In 75% of patients, sites of vascular involvement include the aortic arch and its branches. The most commonly involved aortic branches are the left subclavian artery, which is affected in 55% of patients, followed by the right subclavian artery (38%), the left common carotid artery (30%), and the right common carotid artery (15%).
Aortography most frequently reveals focal, smooth, symmetric narrowing of the aorta and multiple branch vessel stenosis or occlusion, with secondary collateral vascularity or systemic pulmonary shunts. Stenosis, the most common finding, tends to affect the thoracic aorta, the abdominal aorta, the subclavian artery, the common carotid arteries, and the renal arteries. Arterial dilatation and fusiform aneurysms are often found in the ascending aorta and in the right-sided brachiocephalic and subclavian arteries. When TAK involves the subclavian artery, the lesion is a smoothly tapered stenosis; it begins within a few centimeters of the arch and extends to the origin of the vertebral artery. When the condition involves the carotid artery, regions of multisegmental dilatation are alternated with regions of normal-appearing arterial wall. [18]
Serial angiography is helpful not only for initial diagnosis but also for follow-up. In a prospective study, up to 61% of patients with clinically inactive disease developed angiographic changes consistent with persistent inflammatory disease at angiography follow-up. [60]
Pressure measurements in the ascending aorta should be obtained and compared with measurements in the extremities.
Fibromuscular dysplasia (FMD) is part of the differential diagnoses of Takayasu arteritis. Classic FMD has a beaded appearance and usually does not affect the aorta, as evidenced on angiograms. FMD is rare in the subclavian artery.
Angiography has also been used in interventional radiology procedures such as percutaneous transluminal angioplasty (PTA) in patients with quiescent disease and clinical stenosis. PTA without stent placement has revealed long-term patency of 50% at 5 years. [61] Detailed assessment, including disease activity and optimal immunomodulatory treatment, should be completed before these procedures are performed, as restenosis is frequent in patients with active disease.
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Takayasu arteritis. A 48-year-old woman with Takayasu disease. Note the narrowing of the origin of the right subclavian artery and a narrowed small vessel with subsequent aneurysmal dilatation on the right side.
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Takayasu arteritis. Characteristic long, tapered, narrowing of the distal aorta and iliac vessels.
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Takayasu arteritis. Narrowing of the proximal descending aorta and right brachiocephalic artery.
