Abstract
The increasing availability and improvement of imaging techniques are making a profound impact in the evaluation and management of patients with vasculitis, particularly for those with large vessel vasculitis, and will most likely play an ever more important role in the future. Deep, large vessels can be examined by CT or MRI, while ultrasound is the method of choice for the evaluation of superficial vessels (such as temporal, carotid, and axillary arteries). PET is very sensitive in detecting large vessel inflammation, but it does not delineate the vessel wall. Imaging studies can also be used to monitor the disease course and the development of late vascular complication. This review will focus on the role of imaging studies in diagnosing and monitoring LVV, but will also mention their principal applications in medium and small-sized vessel vasculitis. Indications and limitations of the available imaging modalities will be discussed as well.
Introduction
Primary systemic vasculitides are classified by the diameter of the vessels that are predominantly involved. The increasing availability and improvement of imaging techniques are making a profound impact in the evaluation of patients with vasculitis, particularly for those with large vessel vasculitis (LVV), that include giant cell arteritis (GCA), Takayasu arteritis (TAK) and with primary central nervous system vasculitis (PCNSV). Available imaging techniques are ultrasound, computed tomography (CT) and computed tomography angiography (CTA), magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), and 18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET), often co-registered with computerized tomography (PET/CT) . Except for the detection of the characteristic microaneurysms alternating with stenoses in medium-sized vessel vasculitis, digital subtraction angiography (DSA) has become a therapeutic procedure for endovascular intervention in LVV rather than a diagnostic method . Finally, in small vessel vasculitis imaging modalities are usually required to document internal organs involvement . This review will focus on the role of imaging studies in diagnosing and monitoring LVV, but will also mention their principal applications in medium and small-sized vessel vasculitis. Indications and limitations of the available imaging modalities will be discussed as well.
Ultrasound
Large vessel vasculitis
Giant cell arteritis
Ultrasound depicts inflammatory artery wall thickening in LVV similar to MRI and CT. The wall thickening is most commonly concentric in axial views. It appears hypoechoic (darker) compared to the surrounding tissue. However, echogenicity is higher than the anechoic (black) artery lumen. A normal intima-media complex is a homogenous, hypo- or anechoic echostructure delineated by two parallel hyperechoic margins. In case of vasculitis thickened hypoechoic tissue with echogenicity similar to synovitis is found instead of the intima-media complex. This phenomenon has been described as “halo sign” . Furthermore, ultrasound detects stenoses and occlusions in severely involved arteries.
The advantages of ultrasound are:
- •
It can be performed together with history and clinical examination in an outpatient clinical setting or as a bedside procedure .
- •
A suspected diagnosis of GCA can be confirmed in a “fast track clinic” approach within one appointment. Patients and referring physicians do not have to wait for the results .
- •
Equipment is widely available in rheumatology practice as the same ultrasound machines and probes are used for musculoskeletal examination.
- •
Findings can be explained to the patient during the procedure; and additional questions can be asked while the patient is being examined.
- •
The examination is well tolerated by the patients. It has no relevant side effects.
- •
Ultrasound has the highest resolution (100 μm) among all imaging modalities for diagnosing vasculitis. It detects scarce pathology even in small arteries such as the temporal and facial arteries .
- •
Ultrasound allows determining blood flow characteristics in addition to depicting morphology.
- •
Ultrasound is less expensive than other imaging modalities. Costs can be saved when ultrasound replaces biopsy in clear cases .
- •
When compared to other imaging techniques particularly ultrasound in GCA has been evaluated in many studies and several meta-analyses within more than 20 years .
- •
Images and videos of the ultrasound examination can be stored. The review of stored videos by sonographers is as reliable as the review of temporal artery biopsy specimens by pathologists .
In suspected GCA at least the common superficial temporal arteries with their frontal and parietal branches and the axillary arteries should be examined bilaterally. Other arteries such as the facial, occipital, extracranial carotid, vertebral, subclavian, femoral and popliteal arteries can also be easily assessed. A complete examination of all arteries is though time consuming and may be reserved only for special situations, e.g. if diagnosis should not yet be clear after history, clinical examination and ultrasound of temporal and axillary arteries. An experienced sonographer can examine the temporal and axillary arteries in less than 15 min in conjunction with a concise and structured history and clinical examination. The ascending and the abdominal aorta with its branches (coeliac artery, mesenteric and renal arteries) are visible with ultrasound. However, resolution and visibility decrease due to lower frequencies for better penetration. Moreover, air may impair visibility. The descending thoracic aorta can be visualized with trans-oesophageal ultrasound only. Ultrasound can depict abdominal aortitis better than periaortitis. Carotid and femoral arteries are usually arteriosclerotic in the age group of GCA patients. Although arteriosclerosis is irregular and eccentric, it is cannot always be easily differentiated from vasculitis in theses arteries.
Ultrasound is more sensitive than temporal artery biopsy compared to the clinical diagnosis of GCA because a far larger anatomical area can be examined. This is particularly the case in large-vessel GCA in which temporal arteries are not involved in about 40% of cases . On the other hand the diagnosis may be missed by ultrasound in cases with low grade inflammation, i.e. if only adventitial vessels or vasa vasorum are inflamed .
Temporal arteries
Ultrasound can be regarded as an element of the clinical examination. After history and palpation of the temporal arteries the sonographer begins with the ultrasound examination of the temporal arteries. The patient is lying supine looking at the ultrasound monitor. The sonographer begins with the examination of the left common superficial temporal artery anterior to the ear and follows the artery distally to the frontal and parietal branches in longitudinal and transverse planes before the right side is examined similarly. Alternatively the sonographer can start with a segment which appears to be most affected. This may be the case for instance if a frontal branch is indurated and thickened.
A normal superficial temporal artery has an intima-media complex with a diameter of about 0.2 mm ( Fig. 1 ). In acute temporal arteritis the artery wall becomes thickened and hypoechoic (dark) due to vasculitis with edema ( Fig. 2 ). The diameter of the intima-media complex will then be more than 0.4 mm; in most cases the diameter of the halo is 0.5 mm–0.8 mm .
The sonographer should apply low pressure with the probe. Otherwise compressed arteries may become invisible. On the other hand, compression allows differentiating compressible artery lumen from incompressible vasculitic wall swelling . If temporal arteries localize under hair more ultrasound gel needs to be applied; and pressure should be slightly increased for adequately visualizing the arteries.
Ultrasound technology has considerably improved during the last years providing high resolution images and good sensitivity for detecting blood flow with color Doppler mode. It is still advisable to use high-end technology for examining the temporal arteries. A linear probe with a frequency range that includes at least 10 MHz for gray scale sonography and at least 7 MHz for color Doppler sonography should be used. Quality increases with probes of 15 MHz and more. Probes with over 20 MHz provide even better images. The sonographer should have performed at least 30 to 50 ultrasound examinations and should have seen at least 5 patients with active GCA before using ultrasound as a routine procedure for diagnosing GCA .
For examining the temporal arteries the highest available frequency (e.g. 18 MHz) should be used for providing the best resolution. Image depth should be about 1.5 cm. One focus should be localized around 4–5 mm below skin surface. Color Doppler mode should be used with about 50–70% of the gray scale frequency (e.g. 10 MHz) and with a pulse repetition frequency (PRF) of 2–3 KHz. The color box needs to be steered as probe and artery are parallel to each other. A “pseudo-halo” may appear if only the centre of the lumen is colourized due to lower blood flow velocities close to the artery walls. This “pseudo-halo” is anechoic and compressible while a true halo is not compressible similar to synovitis. If the color gain is too high, smaller halos may be missed.
Stenoses are characterized by turbulent flow which remains in the diastole. Pulsed wave Doppler curves show that a maximum systolic flow velocity determined within the stenosis by pulsed wave (pw)-Doppler ultrasound is ≥2 times higher than the flow velocity before or behind the stenosis. With modern high-end technology a “halo sign” is found in most cases at the level of the stenosis. With older technology the finding of a stenosis could increase the sensitivity of ultrasound .
Clinical examination and ultrasound performed by an experienced clinician and sonographer may replace biopsy in clear cases. Biopsies can be performed in ambivalent cases. Intra-operative ultrasound may help the surgeon to definitely harvest a temporal artery particularly if arteries are small. If ultrasound detects localized vasculitis in frontal and parietal branches the surgeon may be asked to harvest the affected segment. Routine guidance of all biopsies by ultrasound, however, does not increase the sensitivity of histology .
The temporal artery wall swelling disappears after two to three weeks with corticosteroid treatment in most patients with a wide range from 2 days to 6 months in some cases . With treatment the echogenicity increases and the diameter decreases. Therefore patients with suspected GCA should be seen as early as possible. CRP and ESR are currently important parameters for follow-up. As GCA might be treated more often with interleukin (IL) – 6 inhibitors in the future ultrasound may gain more importance as an outcome parameter. An OMERACT group is currently defining pathology and testing reliability of ultrasound of temporal and axillary in GCA. Ultrasound will be evaluated as an outcome parameter in a phase III trial of the IL – 6 inhibitor sirukumab in GCA (SIRRESTA trial; NCT02531633).
Large-vessel GCA
Extra-cranial GCA, particularly affecting the supra-aortic arteries, the proximal arm arteries and the aorta, has been defined as large-vessel GCA . Compared to classic cranial GCA, LV-GCA patients are slightly younger, more commonly female, time between outset and diagnosis of the disease is longer, but sight loss is less common . Increased application and quality of imaging shows that extracranial arterial involvement in GCA is much more common than previously assumed. About 50% of the newly diagnosed GCA patients have axillary artery involvement detected by ultrasound . Adding axillary ultrasound to temporal artery ultrasound in a protocol increases the diagnostic yield for GCA in routine practice .
The axillary arteries can be easily and quickly examined with ultrasound. The probe is placed longitudinally in the axilla along the humeral head and neck. This scan is identical with the axillary shoulder scan for detecting glenohumeral joint effusions. The axillary artery localizes either at the level of the humerus or 1–2 cm medially to it. It runs proximally to the circumflexa humeri artery. The area distal to the circumflexa humeri artery is the proximal brachial artery which may also show vasculitis. In order to receive a good color Doppler image the color box needs to be steered as described for the temporal arteries. For evaluating the artery wall with the gray scale image probe and vessel should be as parallel as possible . A normal vessel shows an intima–media complex of about 0.6 mm ( Fig. 3 ). In case of large-vessel vasculitis the artery wall is thickened, usually more than 1.0 mm . Diagnosis is particularly clear if the wall swelling is concentric and has a diameter of 1.5 mm or more ( Fig. 4 ). Axillary arteries may be stenotic or occluded in GCA with collateral circulation. For examining the axillary arteries with ultrasound high frequency probes are also advisable, preferably around 15–18 MHz. As the flow velocities are slightly higher than in temporal arteries the PRF can be increased to 3–4 KHz.
The wall swelling of extracranial arteries remains longer so that the diagnosis of large-vessel GCA can be established also after months and years of treatment in many patients. Follow-up ultrasound examinations allow determining if disease activity had been adequately suppressed. This is the case if the wall thickness decreases or remains unchanged. Low echogenicity and increasing wall thickness or new stenoses indicate active disease. Studies are currently performed to evaluate if increased vessel wall vascularity detected by contrast-enhanced ultrasound (CEUS) correlates with activity of vasculitis . Recently it could be shown that CEUS is able to demonstrate vascular wall neovascularization, which could be considered a potential marker of disease activity ( Fig. 5 ). We recently found a significant correlation between CEUS and 18F-FDG uptake of the carotid arteries, suggesting an association between vascularization and inflammation and supporting the use of CEUS as a cheap and non-invasive method able to detect disease activity in patients with LVV . Larger studies are needed to confirm these initial findings.
Other arteries like the subclavian, common carotid and vertebral arteries can also be easily examined by ultrasound. However, these arteries are rarely affected in GCA without involvement of either the temporal or axillary arteries. Therefore, routinely examining these arteries will not greatly increase the sensitivity of ultrasound. Carotid artery stenoses are rarely caused by GCA. Most stenoses in the age group around 70–75 years are due to arteriosclerosis. However, vasculitic stenoses and occlusions may occur in the vertebral arteries causing cerebral ischemia and stroke .
Polymyalgia rheumatica
About 50% of GCA patients have symptoms of polymyalgia rheumatica (PMR). In at least 15% of patients with “pure” PMR, i.e. polymyalgia without clinical signs of GCA, ultrasound can display vasculitic artery involvement. In addition, in most cases of PMR shoulder and hip ultrasound displays inflammation such as subdeltoid bursitis, biceps tenosynovitis, small glenohumeroid effusions, hip synovitis and trochanteric bursitis. Therefore musculoskeletal ultrasound has been incorporated into the EULAR/ACR classification criteria , particularly for differentiating PMR from similar medical conditions such as shoulder OA, adhesive capsulitis or pain syndromes. The algorithm of the EULAR/ACR classification criteria which includes ultrasound is as sensitive as the algorithm without ultrasound while it is more specific .
Takayasu arteritis
GCA and Takayasu arteritis are similar regarding histology and initial response to treatment. The ultrasound images are also similar to GCA. Takayasu arteritis never affects the temporal arteries. Patients with Takayasu arteritis are much younger at disease outset; they experience more severe flares; and they need treatment for a longer time than GCA patients. Takayasu arteritis usually occurs less symmetrically. It most commonly affects the left subclavian and common carotid arteries. In suspected disease the carotid, subclavian and vertebral arteries should be examined by ultrasound together with the abdominal aorta. In case of arterial hypertension the renal arteries should be also examined . Echocardiography may reveal left-ventricular hypertrophy due to renal arterial hypertension, vasculitis of the ascending aorta, aortic valve insufficiency, pericardial effusion or pulmonary hypertension. Follow-up ultrasound examinations can be performed as done in large-vessel GCA .
Other vasculitides
In vasculitides involving medium sized arteries like Kawasaki’s disease and in polyarteritis nodosa, endovascular ultrasound can also delineate vascular wall swelling . Ultrasound is most commonly used for detecting aneurysms in these diseases, particularly in Kawasaki’s disease which is frequently complicated by coronary artery aneurysms. Kawasaki’s disease most commonly occurs in infants in whom coronary arteries are well visible by ultrasound. Echocardiography is the imaging method of first choice in the diagnosis of Kawasaki’s disease .
Aneurysms of medium sized abdominal arteries are typical for polyarteritis nodosa. These aneurysms are usually too small for being detected by ultrasound. Only few case reports have been published that could demonstrate these findings .
Vasculitis in Behçet’s disease is most commonly characterized by lower extremity deep vein thrombosis. Ultrasound is the imaging method of first choice for this indication. It could be shown that patients with deep vein thrombosis in Behçet’s disease were most commonly males; they had significantly more bilateral involvement, a more contiguous and symmetric pattern, less complete recanalization, and more frequent collateral formation than patients with deep vein thrombosis of other causes . Asymptomatic thrombosis seems to be rare in Behçet’s disease .
Application in clinical practice: the fast-track clinic
Fast-track clinics for the diagnosis of GCA help initiate treatment before complications such as blindness occur. In such clinics, patients receive appointments within 24 h of a working day. Structured history, clinical examination and ultrasound of temporal and axillary arteries are performed by an experienced rheumatologist . Other arteries may be examined depending on clinical findings. The authors, both in Italy and in Germany, have been offering such fast-track clinics for years. Two studies, one from the United Kingdom and one from Norway have recently shown that sight-loss occurred less frequently after introduction of a fast-track clinic. In most cases this allows to clearly determine if GCA is present or not. With increased experience temporal artery biopsy can be reserved for unclear cases .
In the near future fast-track clinics are expected to be established in an increasing number of rheumatology units with expertise in ultrasound and in management of GCA. Patients with suspected GCA should be immediately referred to these centres. In patients with medium or high clinical probability of GCA and positive ultrasound and in patients of low clinical probability and negative ultrasound GCA can be confirmed or ruled out without performing biopsies. There will be still a place for histology for ambivalent cases and for scientific issues.
Ultrasound
Large vessel vasculitis
Giant cell arteritis
Ultrasound depicts inflammatory artery wall thickening in LVV similar to MRI and CT. The wall thickening is most commonly concentric in axial views. It appears hypoechoic (darker) compared to the surrounding tissue. However, echogenicity is higher than the anechoic (black) artery lumen. A normal intima-media complex is a homogenous, hypo- or anechoic echostructure delineated by two parallel hyperechoic margins. In case of vasculitis thickened hypoechoic tissue with echogenicity similar to synovitis is found instead of the intima-media complex. This phenomenon has been described as “halo sign” . Furthermore, ultrasound detects stenoses and occlusions in severely involved arteries.
The advantages of ultrasound are:
- •
It can be performed together with history and clinical examination in an outpatient clinical setting or as a bedside procedure .
- •
A suspected diagnosis of GCA can be confirmed in a “fast track clinic” approach within one appointment. Patients and referring physicians do not have to wait for the results .
- •
Equipment is widely available in rheumatology practice as the same ultrasound machines and probes are used for musculoskeletal examination.
- •
Findings can be explained to the patient during the procedure; and additional questions can be asked while the patient is being examined.
- •
The examination is well tolerated by the patients. It has no relevant side effects.
- •
Ultrasound has the highest resolution (100 μm) among all imaging modalities for diagnosing vasculitis. It detects scarce pathology even in small arteries such as the temporal and facial arteries .
- •
Ultrasound allows determining blood flow characteristics in addition to depicting morphology.
- •
Ultrasound is less expensive than other imaging modalities. Costs can be saved when ultrasound replaces biopsy in clear cases .
- •
When compared to other imaging techniques particularly ultrasound in GCA has been evaluated in many studies and several meta-analyses within more than 20 years .
- •
Images and videos of the ultrasound examination can be stored. The review of stored videos by sonographers is as reliable as the review of temporal artery biopsy specimens by pathologists .
In suspected GCA at least the common superficial temporal arteries with their frontal and parietal branches and the axillary arteries should be examined bilaterally. Other arteries such as the facial, occipital, extracranial carotid, vertebral, subclavian, femoral and popliteal arteries can also be easily assessed. A complete examination of all arteries is though time consuming and may be reserved only for special situations, e.g. if diagnosis should not yet be clear after history, clinical examination and ultrasound of temporal and axillary arteries. An experienced sonographer can examine the temporal and axillary arteries in less than 15 min in conjunction with a concise and structured history and clinical examination. The ascending and the abdominal aorta with its branches (coeliac artery, mesenteric and renal arteries) are visible with ultrasound. However, resolution and visibility decrease due to lower frequencies for better penetration. Moreover, air may impair visibility. The descending thoracic aorta can be visualized with trans-oesophageal ultrasound only. Ultrasound can depict abdominal aortitis better than periaortitis. Carotid and femoral arteries are usually arteriosclerotic in the age group of GCA patients. Although arteriosclerosis is irregular and eccentric, it is cannot always be easily differentiated from vasculitis in theses arteries.
Ultrasound is more sensitive than temporal artery biopsy compared to the clinical diagnosis of GCA because a far larger anatomical area can be examined. This is particularly the case in large-vessel GCA in which temporal arteries are not involved in about 40% of cases . On the other hand the diagnosis may be missed by ultrasound in cases with low grade inflammation, i.e. if only adventitial vessels or vasa vasorum are inflamed .
Temporal arteries
Ultrasound can be regarded as an element of the clinical examination. After history and palpation of the temporal arteries the sonographer begins with the ultrasound examination of the temporal arteries. The patient is lying supine looking at the ultrasound monitor. The sonographer begins with the examination of the left common superficial temporal artery anterior to the ear and follows the artery distally to the frontal and parietal branches in longitudinal and transverse planes before the right side is examined similarly. Alternatively the sonographer can start with a segment which appears to be most affected. This may be the case for instance if a frontal branch is indurated and thickened.
A normal superficial temporal artery has an intima-media complex with a diameter of about 0.2 mm ( Fig. 1 ). In acute temporal arteritis the artery wall becomes thickened and hypoechoic (dark) due to vasculitis with edema ( Fig. 2 ). The diameter of the intima-media complex will then be more than 0.4 mm; in most cases the diameter of the halo is 0.5 mm–0.8 mm .
The sonographer should apply low pressure with the probe. Otherwise compressed arteries may become invisible. On the other hand, compression allows differentiating compressible artery lumen from incompressible vasculitic wall swelling . If temporal arteries localize under hair more ultrasound gel needs to be applied; and pressure should be slightly increased for adequately visualizing the arteries.
Ultrasound technology has considerably improved during the last years providing high resolution images and good sensitivity for detecting blood flow with color Doppler mode. It is still advisable to use high-end technology for examining the temporal arteries. A linear probe with a frequency range that includes at least 10 MHz for gray scale sonography and at least 7 MHz for color Doppler sonography should be used. Quality increases with probes of 15 MHz and more. Probes with over 20 MHz provide even better images. The sonographer should have performed at least 30 to 50 ultrasound examinations and should have seen at least 5 patients with active GCA before using ultrasound as a routine procedure for diagnosing GCA .
For examining the temporal arteries the highest available frequency (e.g. 18 MHz) should be used for providing the best resolution. Image depth should be about 1.5 cm. One focus should be localized around 4–5 mm below skin surface. Color Doppler mode should be used with about 50–70% of the gray scale frequency (e.g. 10 MHz) and with a pulse repetition frequency (PRF) of 2–3 KHz. The color box needs to be steered as probe and artery are parallel to each other. A “pseudo-halo” may appear if only the centre of the lumen is colourized due to lower blood flow velocities close to the artery walls. This “pseudo-halo” is anechoic and compressible while a true halo is not compressible similar to synovitis. If the color gain is too high, smaller halos may be missed.
Stenoses are characterized by turbulent flow which remains in the diastole. Pulsed wave Doppler curves show that a maximum systolic flow velocity determined within the stenosis by pulsed wave (pw)-Doppler ultrasound is ≥2 times higher than the flow velocity before or behind the stenosis. With modern high-end technology a “halo sign” is found in most cases at the level of the stenosis. With older technology the finding of a stenosis could increase the sensitivity of ultrasound .
Clinical examination and ultrasound performed by an experienced clinician and sonographer may replace biopsy in clear cases. Biopsies can be performed in ambivalent cases. Intra-operative ultrasound may help the surgeon to definitely harvest a temporal artery particularly if arteries are small. If ultrasound detects localized vasculitis in frontal and parietal branches the surgeon may be asked to harvest the affected segment. Routine guidance of all biopsies by ultrasound, however, does not increase the sensitivity of histology .
The temporal artery wall swelling disappears after two to three weeks with corticosteroid treatment in most patients with a wide range from 2 days to 6 months in some cases . With treatment the echogenicity increases and the diameter decreases. Therefore patients with suspected GCA should be seen as early as possible. CRP and ESR are currently important parameters for follow-up. As GCA might be treated more often with interleukin (IL) – 6 inhibitors in the future ultrasound may gain more importance as an outcome parameter. An OMERACT group is currently defining pathology and testing reliability of ultrasound of temporal and axillary in GCA. Ultrasound will be evaluated as an outcome parameter in a phase III trial of the IL – 6 inhibitor sirukumab in GCA (SIRRESTA trial; NCT02531633).
Large-vessel GCA
Extra-cranial GCA, particularly affecting the supra-aortic arteries, the proximal arm arteries and the aorta, has been defined as large-vessel GCA . Compared to classic cranial GCA, LV-GCA patients are slightly younger, more commonly female, time between outset and diagnosis of the disease is longer, but sight loss is less common . Increased application and quality of imaging shows that extracranial arterial involvement in GCA is much more common than previously assumed. About 50% of the newly diagnosed GCA patients have axillary artery involvement detected by ultrasound . Adding axillary ultrasound to temporal artery ultrasound in a protocol increases the diagnostic yield for GCA in routine practice .
The axillary arteries can be easily and quickly examined with ultrasound. The probe is placed longitudinally in the axilla along the humeral head and neck. This scan is identical with the axillary shoulder scan for detecting glenohumeral joint effusions. The axillary artery localizes either at the level of the humerus or 1–2 cm medially to it. It runs proximally to the circumflexa humeri artery. The area distal to the circumflexa humeri artery is the proximal brachial artery which may also show vasculitis. In order to receive a good color Doppler image the color box needs to be steered as described for the temporal arteries. For evaluating the artery wall with the gray scale image probe and vessel should be as parallel as possible . A normal vessel shows an intima–media complex of about 0.6 mm ( Fig. 3 ). In case of large-vessel vasculitis the artery wall is thickened, usually more than 1.0 mm . Diagnosis is particularly clear if the wall swelling is concentric and has a diameter of 1.5 mm or more ( Fig. 4 ). Axillary arteries may be stenotic or occluded in GCA with collateral circulation. For examining the axillary arteries with ultrasound high frequency probes are also advisable, preferably around 15–18 MHz. As the flow velocities are slightly higher than in temporal arteries the PRF can be increased to 3–4 KHz.
The wall swelling of extracranial arteries remains longer so that the diagnosis of large-vessel GCA can be established also after months and years of treatment in many patients. Follow-up ultrasound examinations allow determining if disease activity had been adequately suppressed. This is the case if the wall thickness decreases or remains unchanged. Low echogenicity and increasing wall thickness or new stenoses indicate active disease. Studies are currently performed to evaluate if increased vessel wall vascularity detected by contrast-enhanced ultrasound (CEUS) correlates with activity of vasculitis . Recently it could be shown that CEUS is able to demonstrate vascular wall neovascularization, which could be considered a potential marker of disease activity ( Fig. 5 ). We recently found a significant correlation between CEUS and 18F-FDG uptake of the carotid arteries, suggesting an association between vascularization and inflammation and supporting the use of CEUS as a cheap and non-invasive method able to detect disease activity in patients with LVV . Larger studies are needed to confirm these initial findings.
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