High-Resolution MRI in Giant Cell Arteritis: Imaging of the Wall of the Superficial Temporal Artery

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1 Vascular Imaging Bley et al. MRI of Vessel Wall in Giant Cell Arteritis Thorsten A. Bley 1 Oliver Wieben 2 Markus Uhl 1 Jens Thiel 3 Dieter Schmidt 4 Mathias Langer 1 Bley TA, Wieben O, Uhl M, Thiel J, Schmidt D, Langer M Received February 19, 2004; accepted after revision June 21, Department of Diagnostic Radiology, University of Freiburg, Hugstetter Strasse 55, Freiburg, BW 79106, Germany. Address correspondence to T. A. Bley (bley@mrs1.ukl.uni-freiburg.de). 2 Department of Diagnostic Radiology Medical Physics, University of Freiburg, Freiburg, Germany 3 Department of Clinical Immunology and Rheumatology, Univesity of Freiburg, Freiburg, Germany. 4 Department of Ophthalmology, University of Freiburg, Freiburg, Germany. AJR 2005;184: X/05/ American Roentgen Ray Society High-Resolution MRI in Giant Cell Arteritis: Imaging of the Wall of the Superficial Temporal Artery OBJECTIVE. This study investigated the hypothesis that high-resolution MRI can reveal mural inflammatory changes of the superficial temporal artery in giant cell arteritis (GCA). SUBJECTS AND METHODS. MRI of the temporal artery of 20 patients with suspected GCA was performed on a 1.5-T scanner using a dedicated eight-element phased-array head coil. Contrast-enhanced multislice T1-weighted spin-echo sequences were acquired perpendicular to the orientation of the vessel, with a submillimeter spatial resolution of mm and a slice thickness of 3 mm. Mural thickness and lumen diameter of the temporal artery were measured, and mural contrast enhancement was graded on a four-point scale by two radiologists. For all patients, the MRI results were compared with the findings of clinical examination and laboratory tests. In addition, biopsy samples of the temporal artery were taken from 16 of these patients. RESULTS. MRI sharply demonstrated the superficial temporal artery, allowing an evaluation of its lumen and wall. Seventeen patients were GCA-positive according to criteria of the American College of Rheumatology. Of these 17, 16 had true-positive MRI findings and one had false-negative MRI findings. The 3 patients who were GCA-negative according to the American College of Rheumatology criteria had true-negative MRI findings. The mean thickness of the vessel wall and the lumen diameter were 0.88 ± 0.23 mm and 0.78 ± 0.29 mm, respectively, in GCA-positive patients and 0.57 ± 0.25 mm and 0.7 ± 0.1 mm, respectively, in GCA-negative patients. CONCLUSION. High-resolution contrast-enhanced MRI of the temporal artery allowed visualization of the temporal artery and evaluation of possible inflammation of the vessel wall. Our initial results with this noninvasive technique agreed well with histologic results and with the clinical criteria of the American College of Rheumatology. iant cell arteritis (GCA) is a G chronic vasculitis of large- and medium-sized arteries, often associated with polymyalgia rheumatica [1] and with a histologic finding of granulomatous inflammation [2]. The incidence of GCA peaks between the ages of 70 and 80 years [1]. Clinical indications include new onset or new type of headache and tenderness of the temporal artery to palpation. Diplopia, amaurosis fugax, or sudden blindness may occur. Serum values for C-reactive protein are usually elevated above the normal value of < 0.5 mg/dl, and the erythrocyte sedimentation rate according to Westergren can be greater than 50 mm/ hr, in contrast to normal levels, which are < 10 mm in the first hour. Certainty about the correct diagnosis is needed, especially in view of the required long-term treatment with corticosteroids and their side effects. Criteria for classification of GCA were proposed by the American College of Rheumatology (ACR) [3]. Giant cells found at biopsy of the temporal artery are usually required for reliable diagnosis [4]. Inflammation of the affected arteries is often intermittent rather than continuous [1]. Schmidt et al. have reported that a dark halo can be observed in color duplex sonography of the temporal artery in patients with GCA [4]. They hypothesized that this halo is a sign of fluid in the artery wall, and Reinhard et al. found a sensitivity of 73% and a specificity of 93% for duplex sonography compared with findings at histology [5]. Next to CT [6], MRI of the aorta and the supraaortic vessels is the preferred diagnostic tool to exclude aortitis noninvasively [7]. Anatomic information, including lumen configuration and vascular wall thickness, AJR:184, January

2 Bley et al. can be obtained with various obliquities. The degree of wall enhancement and the presence of edema can be evaluated. So far, direct visualization of the temporal artery in GCA has been reported only in case reports cases in which 2D or 3D MR angiography [8, 9] or parasagittal T1-weighted spin-echo imaging [10] had been performed. Recently, we showed a first case of vessel wall imaging of the temporal artery in a patient [11]. In this study, we investigated the hypothesis that high-resolution MRI can reveal mural inflammatory changes of the superficial temporal artery in GCA. A C Fig. 1. Contrast-enhanced MR images of 4 patients with various degrees of mural enhancement of temporal artery (arrows). No or slight enhancement is considered physiologically normal, whereas prominent or strong mural enhancement indicates mural inflammation. Nitroglycerine capsule used as fiducial marker appears as white ball in A and C. A, No enhancement (73-year-old woman). B, Slight enhancement (65-year-old man). C, Prominent enhancement (68-year-old man). D, Strong enhancement (68-year-old man). Subjects and Methods Twenty patients (10 women and 10 men; age range, years; mean age, 72 years) with clinically suspected GCA underwent high-resolution MRI for evaluation of the temporal artery. Written informed consent was obtained from each patient before the MRI investigation. The study was approved by the local ethics review committee and followed the declaration of Helsinki. Two nitroglycerine capsules were placed along the frontal branch of the superficial temporal artery as fiducial markers for identification of the clinically most prominent site of the inflamed vessel on the MRI localizer. High-resolution MRI was performed on a 1.5-T scanner (Magnetom Sonata, Siemens) using a dedicated eight-element phased-array head coil. Multislice T1-weighted spin-echo sequences were acquired perpendicular to the orientation of the vessel, with an acquired submillimeter spatial resolution of mm (TR/TE, 500/22; field of view, mm 2 ; acquisition matrix, ; number of excitations, 1). Eleven slices 3 mm thick and 3 mm apart covered a distance of 63 mm. The acquisition of fat-saturated multislice T1-weighted spin-echo images with identical parameters began approximately 1 min after venous injection of 0.1 mmol of gadolinium-based contrast agent (Magnevist, Schering) per B D 284 AJR:184, January 2005

3 MRI of Vessel Wall in Giant Cell Arteritis kilogram of body weight. MRI was performed before biopsy of the temporal artery. In a consensus reading, two radiologists with different levels of experience in diagnostic radiology (4 and 11 years) evaluated the MRI scans. Neither observer was aware of clinical or laboratory findings. Image-quality criteria, including gray level, image contrast, spatial resolution, and the presence of possible susceptibility artifacts, were rated subjectively. Inflammatory changes such as contrast enhancement of the vessel wall and of the perivascular tissue, thickening of the vessel wall, aneurysm, or dissection of the vessel were evaluated. For ranking of mural contrast enhancement, the following fourpoint scale was used:, no enhancement; +, slight mural enhancement; ++, prominent mural enhancement; and +++, strong mural enhancement, including perivascular tissue. Figure 1 shows an example of each of these categories. No or slight mural enhancement was classified as physiologic, whereas prominent or strong mural enhancement was classified as arteritis. The diameter of the vessel lumen and the thickness of the enhanced wall of the temporal artery were measured electronically using state-of-the-art radiology workstations (J-Vision, TIANI). C-reactive protein level and erythrocyte sedimentation rate were measured for each patient. All patients were initially treated with a therapeutic dose of corticosteroids. On average, the cortisone therapy began 3 days 9 hr. before the MRI investigation. A biopsy of the temporal artery was performed for 16 of the 20 patients after the MRI A Fig. 2. MR images of 73-year-old man with giant cell arteritis. A, Unenhanced high-resolution coronal T1-weighted 2D spin-echo sequence (TR/TE, 500/22; field of view, cm 2 ; acquisition matrix, ) depicts frontal branch of right temporal artery (arrow). B, Contrast-enhanced, fat-saturated T1-weighted 2D spin-echo sequence at same position as A shows bright contrast enhancement of thickened vessel wall, strongly indicating arteritis (arrow). Concomitant bright signal intensity of lumen of temporal vein (arrowheads) and low signal intensity of lumen of temporal artery are due to flow-void phenomenon (arrow) examination as the most reliable way to diagnose GCA. Biopsy specimens were taken from the same frontal branch of the superficial temporal artery as that imaged with MRI. Clinical and laboratory signs of GCA were reevaluated when the patients were receiving corticosteroid medication. Results The images of all patients had good diagnostic quality, and the temporal artery was clearly depicted. The lumen of the temporal veins was bright on enhanced scans, whereas the lumen of the temporal artery showed low signal intensity because of the so-called flowvoid phenomenon. This is caused by the inflow of faster-moving spins in the arteries and helps to differentiate temporal arteries from temporal veins, as depicted in Figure 2. Table 1 summarizes the data obtained from the 17 patients in whom GCA was diagnosed according to the ACR criteria. The enhanced images showed thickening of the wall of the temporal artery and mural contrast enhancement indicating inflammation according to class ++ or +++ in 16 of these 17 patients. One patient had false-negative MRI and histologic findings, but the ACR criteria validated the diagnosis of GCA. The average wall thickness of the inflamed arteries was 0.88 ± 0.23 mm (range, mm), and the average lumen diameter was 0.78 ± 0.29 mm (range, mm). The mean value for C-reactive protein was 10.6 mg/dl (range, mg/dl), and the mean erythrocyte sedimentation rate was 77.5 mm (range, mm) in the first hour. The headache symptoms decreased in all 17 GCA-positive patients after treatment with corticosteroids. Biopsy samples were taken from 15 of these patients and showed 13 to have had true-positive findings and two, false-negative findings. Table 2 summarizes the data from the other 3 patients, in whom GCA had been suspected but was excluded on the basis of their clinical course and the ACR criteria. The average wall thickness of the arteries was 0.57 ± 0.25 mm (range, mm), and the average lumen diameter was 0.7 ± 0.1 mm (range, mm). The mean value for C-reactive protein was 5.6 mg/dl (range, mg/dl), and the mean erythrocyte sedimentation rate was 77.0 mm (range, mm) in the first hour. Discussion This study demonstrated the feasibility of using high-resolution MRI to visualize mural inflammatory changes, even in small arteries. Compared with the diagnosis obtained using the ACR criteria, diagnosis using MRI was true-positive in 16 patients and true-negative in 3 patients. The only patient whose MRI findings were false-negative also had falsenegative histologic findings. It is possible that B AJR:184, January

4 Bley et al. TABLE 1 Sex Age (yr) Detailed Values for MRI Findings in Patients with Giant Cell Arteritis Days of Steroid Use a Contrast Enhancement an unaffected artery was examined at histology and MRI, or GCA might have occurred in vessels outside the field of view of MRI, such as in the occipital arteries. The measurements of the vessel wall and lumen, both inflamed and unaffected, correlated closely to those reported by Schmidt et al. using sonography [4]. They found average values for the wall thickness of the frontal branch of the superficial frontal artery of 0.95 mm (inflamed) and 0.65 mm (unaffected), in comparison with our mean values of 0.88 mm (inflamed) and 0.57 mm (unaffected). Wall Thickness Lumen Diameter C-Reactive Protein (mg/dl) Erythrocyte Sedimentation Rate (mm/hr) Mural contrast enhancement on MRI is a well-recognized sign of acute inflammatory changes [12, 13]. Typically, enhancement persists long after the contrast agent has left the vascular system [13]. Therefore, long T1- weighted sequences of up to 6 min can be used to acquire images with high spatial resolution and sufficient signal-to-noise ratio, as we demonstrated here. The unenhanced images without fat suppression added helpful anatomic information. However, they were not used for the diagnosis and might be omitted in future protocols to reduce total imaging time. Giant Cell Arteritis Validated at Biopsy Improvement with Steroids ACR Criteria F / M / M / F / M / F / M / M / F / No biopsy + + F / F / + + M / M /128 No biopsy + + F / F / F / F / Mean Note. ACR = American College of Rheumatology; + indicates slight mural enhancement, considered physiologically normal; ++ indicates prominent mural enhancement, indicating arteritis; +++ indicates strong mural enhancement, indicating arteritis; minus sign ( ) indicates absent. a Before undergoing MRI. TABLE 2 Sex Age (yr) Detailed Values for MRI Findings in Patients Without Giant Cell Arteritis Days of Steroid Use a Contrast Enhancement Wall Thickness Lumen Diameter C-Reactive Protein (mg/dl) Erythrocyte Sedimentation Rate (mm/hr) Inflammation of the temporal artery has been shown to have a segmental distribution [14, 15]. This may be a reason for false-negative results from biopsies. High-resolution MRI may be used to localize segments with the most intense mural inflammatory changes to determine the best site for biopsy. Potentially, such localization may reduce the number of biopsy specimens falsely negative for inflammation. Achkar et al. [16] concluded that temporal artery biopsies might show arteritis even after more than 14 days of corticosteroid therapy in the presence of clinical indication of active disease. Never- Giant Cell Arteritis Validated at Biopsy Improvement with Steroids ACR Criteria M /82 F / No biopsy + M /110 No biopsy Mean Note. ACR = American College of Rheumatology; + indicates slight mural enhancement, considered physiologically normal; ++ indicates prominent mural enhancement, indicating arteritis; +++ indicates strong mural enhancement, indicating arteritis; minus sign ( ) indicates absent. a Before undergoing MRI. 286 AJR:184, January 2005

5 MRI of Vessel Wall in Giant Cell Arteritis theless, we tried to image the temporal artery as early as possible after initial clinical presentation. For monitoring the activity of inflammation under long-term corticosteroid therapy, repeated biopsy of the temporal artery was recommended by Harbison and colleagues [17]. Eventually, high-resolution MRI of the temporal artery may be used instead of repeated biopsies to monitor mural inflammatory changes under therapy. Recognizing that negative biopsy findings for the temporal artery cannot exclude GCA [15], we used two reference standards: findings of the biopsy alone and clinical criteria as proposed by the ACR. In our study, most biopsy specimens proved the presence of GCA, and clinical findings matched the ACR criteria. Therefore, we are convinced that GCA was the correct diagnosis in those patients. However, our study also had some limitations: First, because this was our initial experience with MRI of GCA, we collected data from only a few patients. Therefore, we did not assess the sensitivity and specificity of the method. Trials using more patients are warranted for statistical purposes and are under way. Second, all patients were referred to us with clinically suspected GCA, and this referral cohort may have led to a referral bias. Nevertheless, the bright contrast enhancement seen in our patients remains a strong sign of mural inflammation. In conclusion, our study showed that highresolution MRI allowed for sharp visualization of the superficial temporal artery and that mural inflammatory changes could be observed in all patients. This promising technique offers information even on small-vessel inflammatory disease and might be useful for assisting with noninvasive diagnosis; evaluating disease severity; and, eventually, performing noninvasive follow-up investigations. Acknowledgments We thank Hans-Hartmut Peter, Peter Vaith, and Jürgen Hennig for their continuing medical and technical advice and support. References 1. Salvarani C, Cantini F, Boiardi L, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med 2002;347: Horton B, Magath T, Brown G. An undescribed form of arteritis of the temporal vessels. Mayo Clin Proc 1932;7: Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990;33: Schmidt WA, Kraft HE, Vorpahl K, Volker L, Gromnica-Ihle EJ. Color duplex ultrasonography in the diagnosis of temporal arteritis. N Engl J Med 1997;337: Reinhard M, Schmidt D, Hetzel A. Color-coded sonography in suspected temporal arteritis: experiences after 83 cases. Rheumatol Int 2003 Nov 5 [Epub ahead of print] 6. Bau JL, Ly JQ, Borstad GC, Lusk JD, Seay TM, Beall DP. Giant cell arteritis. AJR 2003;181: Atalay MK, Bluemke DA. Magnetic resonance imaging of large vessel vasculitis. Curr Opin Rheumatol 2001;13: Mitomo T, Funyu T, Takahashi Y, Murakami K, Koyama K, Kamio K. Giant cell arteritis and magnetic resonance angiography. Arthritis Rheum 1998;41: Harada S, Mitsunobu F, Kodama F, et al. Giant cell arteritis associated with rheumatoid arthritis monitored by magnetic resonance angiography. Intern Med 1999;38: Anders HJ, Sigl T, Sander A, Coppenrath E, Pfluger T, Kellner H. Gadolinium contrast magnetic resonance imaging of the temporal artery in giant cell arteritis. J Rheumatol 1999;26: Bley TA, Wieben O, Leupold J, Uhl M. MRI findings in temporal arteritis. Circulation 2004 (in press) 12. Matsunaga N, Hayashi K, Sakamoto I, et al. Takayasu arteritis: MR manifestations and diagnosis of acute and chronic phase. J Magn Reson Imaging 1998;8: Choe YH, Kim DK, Koh EM, Do YS, Lee WR. Takayasu arteritis: diagnosis with MR imaging and MR angiography in acute and chronic active stages. J Magn Reson Imaging 1999;10: Klein RG, Campbell RJ, Hunder GG, Carney JA. Skip lesions in temporal arteritis. Mayo Clin Proc 1976;51: Hall S, Persellin S, Lie JT, O Brien PC, Kurland LT, Hunder GG. The therapeutic impact of temporal artery biopsy. Lancet 1983;2: Achkar AA, Lie JT, Hunder GG, O Fallon WM, Gabriel SE. How does previous corticosteroid treatment affect the biopsy findings in giant cell (temporal) arteritis? Ann Intern Med 1994;120: Harbison JW, Selhorst JB, Waybright EA, Shipkin PM. Giant cell arteritis. (letter) Lancet 1980;1:1035 AJR:184, January