ClinicalRadiology(1992) 46, 324 328
Fat-Suppression Magnetic Resonance Imaging in the Preoperative Localization of Parathyroid Adenomas A. R. W R I G H T * t , P. R. G O D D A R D * ~ , S. NICHOLSON§, D. C. KINSELLA*$, E. R. DAVIES*¶ and J. R. F A R N D O N §
*Bristol MRI Centre, Frenchay Hospital, "~University Department of Radiology, Royal Victoria Infirmary, Newcastle upon Tyne, ~Department of Radiodiagnosis, Bristol Royal Infirmary; §University Department of Surgery, Bristol Royal Infirmary, and ¶ University Department of Radiodiagnosis, Bristol Royal Infirmary, Bristol Prospective localization of parathyroid adenomas was attempted in 16 patients with hyperparathyroidism prior to surgery. All patients had magnetic resonance imaging (MRI) using Tl-weighted spin-echo (SE) sequences and a fat-suppression sequence, the short-tau inversion recovery (STIR) sequence. Correlation with the results of surgery yielded an overall sensitivity of 71% and a specificity of 94%. Performance was good in patients with previous surgery and with ectopic tumours. We believe that fat-suppression MRI is a valuable technique in the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism. Wright, A.R., Goddard, P.R., Nicholson, S., Kinsella, D.C., Davies, E.R. & Farndon, J.R. (1992). Clinical Radiology 46, 324 328. Fat-Suppression Magnetic Resonance Imaging in the Preoperative Localization of Parathyroid Adenomas
Accepted for Publication 22 July 1992
All studies using MRI to localize parathyroid adenomas have, to date, employed T1- and T2-weighted spin-echo (SE) sequences only. Sensitivities of 64 78% and specificities of 88-95% have been reported [1-6]. The use of intravenous gadolinium-DTPA has not made a significant contribution to lesion detection [7]. The localization of parathyroid tumours using fatsuppression MRI has not previously been assessed. In this study, we have used the STIR sequence, a fat suppression technique which produces images of comparatively low spatial resolution, but with high lesion-detectability. In addition, Tl-weighted SE images were obtained in all patients. The STIR sequence relies on a short inversion-time (TI) to suppress the signal from fat, and to highlight the signal from areas of high tissue-water content. Although STIR images are noisy with comparatively poor anatomical resolution, the STIR sequence does have certain important advantages over the more commonly employed T2weighted SE sequence, namely: (a) High lesion contrast is available as TI- and T2dependent contrast are additive with this sequence [9]. (b) Lesions with prolonged T2 do not become isointense with fat as they may do with T2-weighted SE sequences [2,3,8]. In fact, suppression of the signal from surrounding fat further enhances lesion contrast [9]. (c) Suppression of the fat signal can improve motion artefact [9]. Comparison of the STIR image with the superior anatomical detail of the Tl-weighted SE images in two planes allows a more precise localization of any lesion detected as well as confirmation of its nature. The STIR sequence has already proved useful in Correspondenceto: Dr P. R. Goddard, Departmentof Radiodiagnosis, Bristol Royal Infirmary,Bristol BS2 8HW.
demonstrating lesions in a variety of sites [10 15]. It was therefore decided to evaluate the ability of the STIR sequence to demonstrate parathyroid lesions. MATERIALS AND M E T H O D S Sixteen patients with biochemically proven hyperparathyroidism were studied. There were 11 women and five men, age range 39-77 years, mean age 63.2 years. All patients had raised serum parathormone levels and hypercalcaemia with mean level of corrected serum calcium 3.06 mmol/1, range 2.76 3.80 mmol/1 (normal range 2.50-2.72 mmol/1). All patients had non-specific symptoms referable to hypercalcaemia such as lassitude, anorexia, polydipsia and constipation. Four patients had renal failure; two of these were on haemodialysis for conditions predating their hyperparathyroidism. Four patients had bone pain, including the two patients on dialysis, both of whom showed radiological evidence of renal osteodystrophy. One patient had multiple endocrine neoplasia type 1 (MEN 1) with peptic ulceration, and one had familial parathyroid neoplasia. Five of 16 patients had been previously explored. Two of these had parathyroid adenomas; two had negative explorations and one had surgery for coincidental thyroid disease. Patients were scanned using a Picker Vista 2055 HP 0.5T superconducting system using the body coil both to transmit and receive radiofrequency (RF) signal. All patients were scanned from hyoid bone to tracheal bifurcation using 8 mm contiguous slices. The majority of patients had the following sequences: (a) Coronal Tl-weighted SE sequences (TR 500/TE 26) with a field of view (FOV) of 35 cm and horizontal phase-encoding. (b) Axial Tl-weighted SE sequences (TR 500/TE 26)
325
MRI OF PARATHYROID ADENOMAS
with 25 28 cm F O V for the neck and 32-35 cm FOV for the chest and vertical phase-encoding. (c) Axial STIR sequences (TR 1500/TI 100/TE 30) with FOV and phase-encoding direction similar to the axial Tl-weighted SE sequences. Data were acquired using two-dimensional Fourier transform onto a 256 × 200 matrix with four R F excitations per phase-encoding step for the Tl-weighted sequences and two for the S T I R sequences. Interpolation to 512 x 512 matrix was employed for viewing purposes. At surgery, all four parathyroid glands were located where possible. Any single adenoma was completely excised and comparative biopsies taken from normal glands. In the case of hyperplastic glands, three were excised along with a portion of the fourth. All patients, bar one, became normocalcaemic following surgery. All tissue excised at surgery was submitted for histological analysis in order to confirm the operative diagnosis. Stark e t al. [16] have shown that abnormal parathyroid glands exhibit increased T1- and T2-relaxation times. This is consistent with subsequent studies which have shown that parathyroid lesions generally have low or equal intensity relative to muscle on Tl-weighted images, and increased intensity on T2-weighted images [2-4]. It was therefore expected that abnormal parathyroid glands would show high signal on STIR sequences. The diagnosis of a lesion was based on the presence of a discrete highsignal area on the S T I R sequence that was: (a) in a position that could correspond to an abnormal parathyroid gland; (b) not accounted for by some other highsignal structure such as the oesophagus or a blood vessel; and (c) confirmed by a medium-intensity lesion in the same site on the Tl-weighted images. In general, the S T I R images were used for lesion detection, and the T1weighted images for confirmation and more precise anatomical localization of the lesion. Magnetic resonance images were interpreted prospectively without access to clinical details or results of surgery. Specificity and sensitivity calculations were based on the prospective reporting compared with histological findings. In each patient, three regions were evaluated separately. Regions L and R were defined as posterior to and contiguous with left or right thyroid lobe respectively, and region M as mediastinal or otherwise ectopic. In order to be counted as true-positive, any lesion had not only to be detected, but also to be allocated to the correct region (L, R or M) when compared with the surgical findings. In the case of mediastinal/ectopic lesions, the precise site had to be specified. The results are therefore based on 48 potential sites for the lesions in the 16 patients. Following correlation of imaging results with the findings at surgery, a second reading of the M R images was made with the other clinical information available. Particular attention was paid to the false-negative and false-positive calls to see if sensitivity or specificity could be improved retrospectively.
geal lesion showing nodular hyperplasia, the other glands being normal. Five patients had abnormal glands in region M; 10 had abnormal glands in regions L or R. Glands ranged in size from 470 mg to 3 g. Figure 1 shows the appearance of a 0.9 g lesion in the superior mediastinum posterior to the left clavicle, and Fig. 2 a smaller orthotopic lesion in the right upper position. The S T I R and Tl-weighted sequences are complementary in identifying and accurately localizing the lesions. Table 1 shows the results of the prospective analysis of the M R I studies and of surgery. Table 2 shows the cumulative results of M R I (true-positive, false-negative, etc) for each region along with calculated sensitivities and specificities for the patients as a whole, as well as for specific sub-groups of patients.
RESULTS
DISCUSSION
Twelve patients had single adenomas; none had multiple adenomas. One patient had an adenoma in the left upper position, a normal right upper gland and hyperplasia of the lower two glands; one patient had four-gland hyperplasia; and the M E N 1 patient had a paraoesopha-
In a previously unexplored patient with hyperparathyroidism, an experienced surgeon has a 95 98% chance of successful treatment without prior imaging localization of the abnormal parathyroid glands [17,18]. The need for imaging before a first exploration is thus open to
(a)
(b) Fig. 1 Left superior mediastinal adenoma (arrow) well shown on STIR image (a) and distinct from mediastinal fat. T l-weighted image (b) allows more precise anatomical localization.
326
CLINICAL RADIOLOGY Table 2 - Cumulative results of magnetic resonance imaging studies for localizing parathyroid lesions by region in patients with hyperparathyroid. ism L
R
M
All
4 l 2 9
4 3 0 9
4 l 0 11
12 5 2 29
4 1 0 6
3 2 0 6
2 1 0 8
9 4 0 20
0 0 2 3
1 1 0 3
2 0 0 3
3 I 2 9
1 1 0 6
4 1 0 3
5 2 2 15
All patients
TP FN FP TN Sensitivity = 71% Specificity - 94% No previous surgery
TP FN FP TN Sensitivity = 69 % Specificity = 100%
(a)
Previous surgery
TP FN FP TN Sensitivity = 75% Specificity - 82%
Previous surgery and/or eetopic lesions
TP FN FP TN Sensitivity = 71% Specificity=88% '
0 0 2 6
TP, True-positive; FN, false-negative; FP, false-positive; TN, truenegative; L, region L; R, region R; M, ectopic lesion.
(b) Fig. 2 - The right-sided adenoma (black arrow) is well shown adjacent to the oesophagus with the STIR sequence (a). The oseophagus is seen as a high-signal structure (open black arrow) and can be distinguished from an adenoma by its appearance on consecutive scans and by comparison with the Tl-weighted scan (b). The STIR image (a) also shows motion artefact in the phase-encoding direction emanating from vessels (white arrowheads). Note the variable appearance of the carotid arteries (white arrows) and the jugular veins (curved white arrows).
Table 1 - Results of prospective analysis of magnetic resonance imaging compared with surgical findings in 16 patients with hyperparathyroidism Patient
MRI
Surgery
1" 2* 3* 4* 5* 6 7 8 9 10
M L, R L M Neg Neg M M R L
11 12 13 14 15 16
Neg L L R L R
M R Neg M R M M M (nodular HP) R L (upper); L, R (lower) HP 4-gland HP L L R L R
L, Lesion in region L; R, lesion in region R; M, lesion in region M; * patient with previous surgery; Neg, lesion not identified; HP, hyperplasia.
q u e s t i o n . I n p r e v i o u s l y explored p a t i e n t s o n the o t h e r h a n d , success rates o f r e o p e r a t i o n are m u c h lower (typically 65%); s u r g e r y is technically difficult a n d time c o n s u m i n g ; a n d significant c o m p l i c a t i o n s m o r e c o m m o n [19,20]. I n a d d i t i o n , ectopic t u m o u r s are m o r e likely in this g r o u p . It is g e n e r a l l y accepted that, in these p a t i e n t s , p r i o r i m a g i n g l o c a l i z a t i o n is e x t r e m e l y v a l u a b l e to the surgeon. It follows t h a t the clinical utility o f a n i m a g i n g test m a y d e p e n d o n its s e n s i t i v i t y a n d specificity i n s h o w i n g lesions in difficult sites. T h i s series o f p a t i e n t s i n c l u d e s a high p r o p o r t i o n o f ' p r o b l e m cases' i n c l u d i n g r e o p e r a t i o n s a n d ectopic t u m o u r s , a n d is t h u s typical o f cases p r e s e n t i n g to a t e r t i a r y referral centre. M a g n e t i c r e s o n a n c e i m a g i n g u s i n g the S T I R s e q u e n c e in c o n j u n c t i o n w i t h T l - w e i g h t e d scans h a s p r o d u c e d g o o d overall results in this h e t e r o g e n e o u s g r o u p o f p a t i e n t s . I n t e r e s t i n g l y , the sensitivity o f M R I u s i n g the S T I R s e q u e n c e is very similar w h e t h e r t h e t e c h n i q u e is u s e d i n p a t i e n t s w i t h o r w i t h o u t p r e v i o u s s u r g e r y , o r with t u m o u r s in e c t o p i c sites ( T a b l e 2). I n d e e d , n o statistically significant difference was o b s e r v e d b e t w e e n p e r f o r m a n c e o f M R I in u n o p e r a t e d a n d p r e v i o u s l y o p e r a t e d p a t i e n t s u s i n g a b i n o m i a l m e t h o d ( P = 0 . 0 7 , 0.93 a n d 0.30 for r e g i o n s L, R a n d M respectively), a l t h o u g h n u m b e r s are small a n d these c a l c u l a t i o n s s h o u l d be i n t e r p r e t e d w i t h caution. Nevertheless, fat-suppression MRI appears a p r o m i s i n g t e c h n i q u e for p a r a t h y r o i d l o c a l i z a t i o n irrespective o f surgical s t a t u s o r t u m o u r site. T h i s c o n t r a s t s w i t h the p e r f o r m a n c e o f u l t r a s o u n d a n d
MRI OF P A R A T H Y R O I D A D E N O M A S
thallium-technetium subtraction scintigraphy in patients with prior neck surgery or ectopic lesions. With ultrasound, sensitivities of 32 57% are typical in patients with previous neck surgery [5,21-24]. This is due to loss of the normal tissue planes in the neck and disruption of anatomical landmarks as well as the increased likelihood of ectopic adenomas in this group. Ultrasound is virtually useless for mediastinal adenomas because of the lack of an acoustic window. Thallium-technetium subtraction scintigraphy is also less effective in previously explored patients with sensitivities of 27-68% [5,24,25]. It is also less reliable with mediastinal lesions due to increased background activity and low photon energy [26,27]. Thus, these two techniques perform relatively poorly in the very patients in whom prior localization is of most value to the surgeon. Magnetic resonance imaging has shown high specificity for parathyroid adenoma detection in this series. This is a reflection of the high prevalence of hyperparathyroidism in the study group (100% by definition), and of the fact that normal parathyroid glands are generally not detected. In fact, all imaging techniques are liable to falsepositives from, for example, thyroid nodules and lymph nodes, and in a broader population would be relatively non-specific. Analysis of the false-negative M R I cases shows poor results with hyperptastic glands. Case 10 was a patient with renal failure in whom a left upper position adenoma was identified, but hyperplasia of left and right lower glands missed. The glands were relatively small, being 8 mm and 4 mm in maximum diameter respectively. Hyperplastic glands are generally smaller than adenomas and this no doubt explains their lower detection rate with all imaging techniques. A second patient (Case 11) had renal failure and hyperplasia in four glands, all undetected with M R I despite reasonable size. This patient had coronal STIR sequences only. The coronal STIR was generally considered difficult to interpret and was subsequently abandoned in favour of axial slices. On review of this case following surgery, two discrete high signal lesions were visible adjacent to the thyroid representing two o f the hyperplastic glands. The other patient with an hyperplastic gland (a solitary nodule in an ectopic position) was localized with MRI. The other two false-negative results were single adenomas which were visible in retrospect. One of these was the smallest gland in the series (470 mg), and the other falsenegative lesion was clearly visible on review. The detection rate was thus improved on second reading with increased experience and confidence in the technique. Of the two false-positive cases, the first had a rightsided adenoma (detected by MRI) removed at her second neck exploration. The STIR images showed a further putative lesion on the left but this area was not reexplored. Following surgery, the patient became normocalcaemie and has remained so. The latter M R I abnormality was therefore regarded as false-positive. This patient also had venous sampling which strongly localized to the right. On review of the M R images, the falsepositive lesion was attributed to asymmetry of a generally high-signal thyroid gland. In the second false-positive case, an unusual appearance of the left internal jugular vein was thought to represent a parathyroid adenoma. In general, falsepositives due to blood vessels should be unusual since: (a)
327
vessels can be traced across several slices and may show variable signal characteristics in different slices; (b) when they exhibit high signal, this is usually very intense, more so than tumours; and (c) they are usually accompanied by a motion artefact in the phase-encoding direction (Fig. 2). The overall sensitivity and specificity of M RI using the STIR sequence in conjunction with Tl-weighted SE sequences are comparable with the figures quoted in the literature for conventional M R I using T1- and T2weighted SE sequences [1-6]. This suggests that the two techniques are broadly equivalent. However, we have been unable directly to compare the performance of the STIR sequence for parathyroid adenoma detection with that ofT2-weighted SE sequences since the latter were not carried out in all cases. It is possible that the two techniques have specific strengths and weaknesses. For example, the STIR sequence, being a fat-suppression technique, is likely to be superior for lesions surrounded by fat since adenomas on T2-weighted SE sequences may be isointense with fat and therefore difficult to demonstrate [2,3,8,9]. This raises the question of whether sensitivity could be increased still further by the combination of fat-suppression sequences and T2-weighted scans. In conclusion, M R imaging using a fat-suppression technique (STIR) in conjunction with Tl-weighted sequences gives good results in an heterogeneous group of patients including previously operated patients and those with lesions in ectopic sites. The method as described is quick and straightforward and gives a comprehensive survey of neck and mediastinum in an average examination time of around 45 min. Magnetic resonance imaging using the STIR sequence is a valuable technique in the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism. Acknowledgements. This project was funded with a grant from the Bristol United Hospitals District Medical Research Committee. MRI facilities wereprovidedby the Bristol MRI ScannerFund and the Dawn James Trust. We thank the staff of the Bristol MRI Centre and the Department of Radiodiagnosis, Bristol Royal Infirmary, for tfieir professional assistance, and also Miss AudreyKellett for preparing the illustrations and Mrs Jan Stoddart for typing the manuscript.
REFERENCES
1 Kier R, Blinder RA, Herfkens RJ, Leight GS, Spritzer CE, Carroll BA. MR imaging with surface coils in primary hyperparathyroidism. Journal of Computer Assisted Tomography 1987;11:863 868. 2 Kneeland JB, Krubsack AJ, Lawson TL, Wilson SD, Collier BD, Froncisz et al. Enlarged parathyroid glands: high-resolution local coil MR imaging. Radiology 1987;162:143-146. 3 Peck WW, HigginsCB, Fisher MR, Ling M, Okerlund MD, Clark OH. Hyperparathyroidism:comparisonof MR imagingwith radionuclide scanning. Radiology 1987;t 63:415-420. 4 Spritzer CE, Gefter WB, Hamilton R, Greenberg BM, Axel L, Kressel HY. Abnormal parathyroid glands: high-resolution MR imaging. Radiology 1987;162:487-491. 5 Auffermann W, Gooding GAW, Okerlund MD, Clark OH, Thurnher S, Levin KE et al. Diagnosis of recurrent hyperparathyroidism: comparison of MR imaging and other imaging techniques. American Journal of Roentg enology 1988;150:1027-1033. 6 von Schulthess GK, Weder W, Goebel N, Buchmann P, Gadze A, AugustinyN et al. 1.5TMRI, CT, ultrasonographyand scintigraphy in hyperparathyroidism. European Journal of Radiology 1988;8: 157-164. 7 Seelos KC, DeMarco R, Clark OH, Higgins CB. Persistent and recurrent hyperparathyroidism: assessment with gadopentate dimeglumine-enhanced MR imaging. Radiology 1990;177:373 378. 8 Higgins CB, Auffermann W. MR imaging of thyroid and parathyroid glands: a review of current status. American Journal of Roentgenology 1988;151:1095 1106.
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9 Bydder GM, Young IR. MR imaging: clinical use of the inversion recovery sequence. Journal of Computer Assisted Tomography 1985;9:659 675. 10 Bydder GM, Steiner RE, Blumgart LH, Khenia S, Young IR. MR imaging of the liver using short TI inversion recovery sequences. Journal of Computer Assisted Tomography 1985;9:1084 1089. 11 Graif M, Leung AW-L, Steiner RE, Young IR. Magnetic resonance imaging of the retroperitoneum. Clinical Radiology 1986;37: 441 449. 12 Johnson G, Miller DH, MacManus D, Tofts PS, Barnes D, du Boulay EPGH et al. STIR sequences in NMR imaging of the optic nerve. Neuroradiology 1987;29:238-245. 13 Deans HE, Redpath TW, Smith FW, Parekh S, Forrester JV. Magnetic resonance imaging of the orbits using a binocular surface coil. British Journal of Radiology 1988;61:665 672. 14 Shuman WP, Baron RL, Peters M J, Tazioli PK. Comparison of STIR and spin-echo MR imaging at 1.5T in 90 lesions of the chest, liver and pelvis. American Journal of RoentgenoIogy 1989;152:853 859. 15 Kabala J, Goddard P, Cook P. Magnetic resonance imaging of extracranial head and neck tumours. British Journal of Radiology (in press). 16 Stark DD, Moss AA, Gamsu G, Clark OH, Gooding GAW, Webb WR. Magnetic resonance imaging of the neck. Part II: pathologic findings. Radiology 1984;150:455 461. 17 Satava RM, Beahrs OH, Scholz DA. Success rate of cervical exploration for hyperparathyroidism. Archives of Surgery 1975;110:625 628. 18 Thompson NW, Eckhauser FE, Harness JK. The anatomy of
primary hyperparathyroidism. Surgery 1982;92:814 821. 19 Beazley RM, Costa J, Ketcham AS. Reoperative parathyroid surgery. American Journal of Surgery 1975;130:427 429. 20 Edis A J, Sheedy PF, Beahrs OH, van Heerden JA. Results of reoperation for hyperparathyroidism, with evaluation of preoperative localisation studies. Surgery 1978;84:384 393. 21 Krudy AG, Shawker TH, Doppman JL, Horvath K, Schneider PD, Norton JA el al. Ultrasonic parathyroid localisation in previously operated patients. Clinical Radiology 1984;35:113-118. 22 Stark DD, Gooding GAW, Moss AA, Clark OH, Ovenfors C-O. Parathyroid imaging: comparison of high-resolution CT and highresolution sonography. American Journal of Roentgenology 1983;141:633 638. 23 Clark OH, Okerlund MD, Moss AA, Stark D, Norman D, Newton TH et al. Localisation studies in patients with persistent or recurrent hyperparathyroidism. Surgery 1985;98:1083-1094. 24 Miller DL, Doppman JL, Shawker TH, Krudy AG, Norton JA, Vucich JJ et al. Localisation of parathyroid adenomas in patients who have undergone surgery. Part 1. Noninvasive imaging methods. Radiology 1987;162:133 137. 25 Gooding GAW, Okerlund MD, Stark DD, Clark OH. Parathyroid imaging: comparison of double-tracer (T1-201, Tc-99m) scintigraphy and high-resolution US. Radiology 1986;161:57 64. 26 Wheeler MH, Harrison BJ, French AP, Leach KG. Preliminary results of thallium 201 and technetium 99m scanning of parathyroid glands. Surgery 1984;96:1078-108 I. 27 Skibber JM, Reynolds JC, Spiegel AM, Marx SJ, Fitzpatrick LA, Aurbach GD et al. Computerised technetium/thallium scans and parathyroid reoperation. Surgery 1985;98:1077 1082.
Fat-Suppression Magnetic Resonance Imaging in the Preoperative Localization of Parathyroid Adenomas A. R. W R I G H T * t , P. R. G O D D A R D * ~ , S. NICHOLSON§, D. C. KINSELLA*$, E. R. DAVIES*¶ and J. R. F A R N D O N §
*Bristol MRI Centre, Frenchay Hospital, "~University Department of Radiology, Royal Victoria Infirmary, Newcastle upon Tyne, ~Department of Radiodiagnosis, Bristol Royal Infirmary; §University Department of Surgery, Bristol Royal Infirmary, and ¶ University Department of Radiodiagnosis, Bristol Royal Infirmary, Bristol Prospective localization of parathyroid adenomas was attempted in 16 patients with hyperparathyroidism prior to surgery. All patients had magnetic resonance imaging (MRI) using Tl-weighted spin-echo (SE) sequences and a fat-suppression sequence, the short-tau inversion recovery (STIR) sequence. Correlation with the results of surgery yielded an overall sensitivity of 71% and a specificity of 94%. Performance was good in patients with previous surgery and with ectopic tumours. We believe that fat-suppression MRI is a valuable technique in the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism. Wright, A.R., Goddard, P.R., Nicholson, S., Kinsella, D.C., Davies, E.R. & Farndon, J.R. (1992). Clinical Radiology 46, 324 328. Fat-Suppression Magnetic Resonance Imaging in the Preoperative Localization of Parathyroid Adenomas
Accepted for Publication 22 July 1992
All studies using MRI to localize parathyroid adenomas have, to date, employed T1- and T2-weighted spin-echo (SE) sequences only. Sensitivities of 64 78% and specificities of 88-95% have been reported [1-6]. The use of intravenous gadolinium-DTPA has not made a significant contribution to lesion detection [7]. The localization of parathyroid tumours using fatsuppression MRI has not previously been assessed. In this study, we have used the STIR sequence, a fat suppression technique which produces images of comparatively low spatial resolution, but with high lesion-detectability. In addition, Tl-weighted SE images were obtained in all patients. The STIR sequence relies on a short inversion-time (TI) to suppress the signal from fat, and to highlight the signal from areas of high tissue-water content. Although STIR images are noisy with comparatively poor anatomical resolution, the STIR sequence does have certain important advantages over the more commonly employed T2weighted SE sequence, namely: (a) High lesion contrast is available as TI- and T2dependent contrast are additive with this sequence [9]. (b) Lesions with prolonged T2 do not become isointense with fat as they may do with T2-weighted SE sequences [2,3,8]. In fact, suppression of the signal from surrounding fat further enhances lesion contrast [9]. (c) Suppression of the fat signal can improve motion artefact [9]. Comparison of the STIR image with the superior anatomical detail of the Tl-weighted SE images in two planes allows a more precise localization of any lesion detected as well as confirmation of its nature. The STIR sequence has already proved useful in Correspondenceto: Dr P. R. Goddard, Departmentof Radiodiagnosis, Bristol Royal Infirmary,Bristol BS2 8HW.
demonstrating lesions in a variety of sites [10 15]. It was therefore decided to evaluate the ability of the STIR sequence to demonstrate parathyroid lesions. MATERIALS AND M E T H O D S Sixteen patients with biochemically proven hyperparathyroidism were studied. There were 11 women and five men, age range 39-77 years, mean age 63.2 years. All patients had raised serum parathormone levels and hypercalcaemia with mean level of corrected serum calcium 3.06 mmol/1, range 2.76 3.80 mmol/1 (normal range 2.50-2.72 mmol/1). All patients had non-specific symptoms referable to hypercalcaemia such as lassitude, anorexia, polydipsia and constipation. Four patients had renal failure; two of these were on haemodialysis for conditions predating their hyperparathyroidism. Four patients had bone pain, including the two patients on dialysis, both of whom showed radiological evidence of renal osteodystrophy. One patient had multiple endocrine neoplasia type 1 (MEN 1) with peptic ulceration, and one had familial parathyroid neoplasia. Five of 16 patients had been previously explored. Two of these had parathyroid adenomas; two had negative explorations and one had surgery for coincidental thyroid disease. Patients were scanned using a Picker Vista 2055 HP 0.5T superconducting system using the body coil both to transmit and receive radiofrequency (RF) signal. All patients were scanned from hyoid bone to tracheal bifurcation using 8 mm contiguous slices. The majority of patients had the following sequences: (a) Coronal Tl-weighted SE sequences (TR 500/TE 26) with a field of view (FOV) of 35 cm and horizontal phase-encoding. (b) Axial Tl-weighted SE sequences (TR 500/TE 26)
325
MRI OF PARATHYROID ADENOMAS
with 25 28 cm F O V for the neck and 32-35 cm FOV for the chest and vertical phase-encoding. (c) Axial STIR sequences (TR 1500/TI 100/TE 30) with FOV and phase-encoding direction similar to the axial Tl-weighted SE sequences. Data were acquired using two-dimensional Fourier transform onto a 256 × 200 matrix with four R F excitations per phase-encoding step for the Tl-weighted sequences and two for the S T I R sequences. Interpolation to 512 x 512 matrix was employed for viewing purposes. At surgery, all four parathyroid glands were located where possible. Any single adenoma was completely excised and comparative biopsies taken from normal glands. In the case of hyperplastic glands, three were excised along with a portion of the fourth. All patients, bar one, became normocalcaemic following surgery. All tissue excised at surgery was submitted for histological analysis in order to confirm the operative diagnosis. Stark e t al. [16] have shown that abnormal parathyroid glands exhibit increased T1- and T2-relaxation times. This is consistent with subsequent studies which have shown that parathyroid lesions generally have low or equal intensity relative to muscle on Tl-weighted images, and increased intensity on T2-weighted images [2-4]. It was therefore expected that abnormal parathyroid glands would show high signal on STIR sequences. The diagnosis of a lesion was based on the presence of a discrete highsignal area on the S T I R sequence that was: (a) in a position that could correspond to an abnormal parathyroid gland; (b) not accounted for by some other highsignal structure such as the oesophagus or a blood vessel; and (c) confirmed by a medium-intensity lesion in the same site on the Tl-weighted images. In general, the S T I R images were used for lesion detection, and the T1weighted images for confirmation and more precise anatomical localization of the lesion. Magnetic resonance images were interpreted prospectively without access to clinical details or results of surgery. Specificity and sensitivity calculations were based on the prospective reporting compared with histological findings. In each patient, three regions were evaluated separately. Regions L and R were defined as posterior to and contiguous with left or right thyroid lobe respectively, and region M as mediastinal or otherwise ectopic. In order to be counted as true-positive, any lesion had not only to be detected, but also to be allocated to the correct region (L, R or M) when compared with the surgical findings. In the case of mediastinal/ectopic lesions, the precise site had to be specified. The results are therefore based on 48 potential sites for the lesions in the 16 patients. Following correlation of imaging results with the findings at surgery, a second reading of the M R images was made with the other clinical information available. Particular attention was paid to the false-negative and false-positive calls to see if sensitivity or specificity could be improved retrospectively.
geal lesion showing nodular hyperplasia, the other glands being normal. Five patients had abnormal glands in region M; 10 had abnormal glands in regions L or R. Glands ranged in size from 470 mg to 3 g. Figure 1 shows the appearance of a 0.9 g lesion in the superior mediastinum posterior to the left clavicle, and Fig. 2 a smaller orthotopic lesion in the right upper position. The S T I R and Tl-weighted sequences are complementary in identifying and accurately localizing the lesions. Table 1 shows the results of the prospective analysis of the M R I studies and of surgery. Table 2 shows the cumulative results of M R I (true-positive, false-negative, etc) for each region along with calculated sensitivities and specificities for the patients as a whole, as well as for specific sub-groups of patients.
RESULTS
DISCUSSION
Twelve patients had single adenomas; none had multiple adenomas. One patient had an adenoma in the left upper position, a normal right upper gland and hyperplasia of the lower two glands; one patient had four-gland hyperplasia; and the M E N 1 patient had a paraoesopha-
In a previously unexplored patient with hyperparathyroidism, an experienced surgeon has a 95 98% chance of successful treatment without prior imaging localization of the abnormal parathyroid glands [17,18]. The need for imaging before a first exploration is thus open to
(a)
(b) Fig. 1 Left superior mediastinal adenoma (arrow) well shown on STIR image (a) and distinct from mediastinal fat. T l-weighted image (b) allows more precise anatomical localization.
326
CLINICAL RADIOLOGY Table 2 - Cumulative results of magnetic resonance imaging studies for localizing parathyroid lesions by region in patients with hyperparathyroid. ism L
R
M
All
4 l 2 9
4 3 0 9
4 l 0 11
12 5 2 29
4 1 0 6
3 2 0 6
2 1 0 8
9 4 0 20
0 0 2 3
1 1 0 3
2 0 0 3
3 I 2 9
1 1 0 6
4 1 0 3
5 2 2 15
All patients
TP FN FP TN Sensitivity = 71% Specificity - 94% No previous surgery
TP FN FP TN Sensitivity = 69 % Specificity = 100%
(a)
Previous surgery
TP FN FP TN Sensitivity = 75% Specificity - 82%
Previous surgery and/or eetopic lesions
TP FN FP TN Sensitivity = 71% Specificity=88% '
0 0 2 6
TP, True-positive; FN, false-negative; FP, false-positive; TN, truenegative; L, region L; R, region R; M, ectopic lesion.
(b) Fig. 2 - The right-sided adenoma (black arrow) is well shown adjacent to the oesophagus with the STIR sequence (a). The oseophagus is seen as a high-signal structure (open black arrow) and can be distinguished from an adenoma by its appearance on consecutive scans and by comparison with the Tl-weighted scan (b). The STIR image (a) also shows motion artefact in the phase-encoding direction emanating from vessels (white arrowheads). Note the variable appearance of the carotid arteries (white arrows) and the jugular veins (curved white arrows).
Table 1 - Results of prospective analysis of magnetic resonance imaging compared with surgical findings in 16 patients with hyperparathyroidism Patient
MRI
Surgery
1" 2* 3* 4* 5* 6 7 8 9 10
M L, R L M Neg Neg M M R L
11 12 13 14 15 16
Neg L L R L R
M R Neg M R M M M (nodular HP) R L (upper); L, R (lower) HP 4-gland HP L L R L R
L, Lesion in region L; R, lesion in region R; M, lesion in region M; * patient with previous surgery; Neg, lesion not identified; HP, hyperplasia.
q u e s t i o n . I n p r e v i o u s l y explored p a t i e n t s o n the o t h e r h a n d , success rates o f r e o p e r a t i o n are m u c h lower (typically 65%); s u r g e r y is technically difficult a n d time c o n s u m i n g ; a n d significant c o m p l i c a t i o n s m o r e c o m m o n [19,20]. I n a d d i t i o n , ectopic t u m o u r s are m o r e likely in this g r o u p . It is g e n e r a l l y accepted that, in these p a t i e n t s , p r i o r i m a g i n g l o c a l i z a t i o n is e x t r e m e l y v a l u a b l e to the surgeon. It follows t h a t the clinical utility o f a n i m a g i n g test m a y d e p e n d o n its s e n s i t i v i t y a n d specificity i n s h o w i n g lesions in difficult sites. T h i s series o f p a t i e n t s i n c l u d e s a high p r o p o r t i o n o f ' p r o b l e m cases' i n c l u d i n g r e o p e r a t i o n s a n d ectopic t u m o u r s , a n d is t h u s typical o f cases p r e s e n t i n g to a t e r t i a r y referral centre. M a g n e t i c r e s o n a n c e i m a g i n g u s i n g the S T I R s e q u e n c e in c o n j u n c t i o n w i t h T l - w e i g h t e d scans h a s p r o d u c e d g o o d overall results in this h e t e r o g e n e o u s g r o u p o f p a t i e n t s . I n t e r e s t i n g l y , the sensitivity o f M R I u s i n g the S T I R s e q u e n c e is very similar w h e t h e r t h e t e c h n i q u e is u s e d i n p a t i e n t s w i t h o r w i t h o u t p r e v i o u s s u r g e r y , o r with t u m o u r s in e c t o p i c sites ( T a b l e 2). I n d e e d , n o statistically significant difference was o b s e r v e d b e t w e e n p e r f o r m a n c e o f M R I in u n o p e r a t e d a n d p r e v i o u s l y o p e r a t e d p a t i e n t s u s i n g a b i n o m i a l m e t h o d ( P = 0 . 0 7 , 0.93 a n d 0.30 for r e g i o n s L, R a n d M respectively), a l t h o u g h n u m b e r s are small a n d these c a l c u l a t i o n s s h o u l d be i n t e r p r e t e d w i t h caution. Nevertheless, fat-suppression MRI appears a p r o m i s i n g t e c h n i q u e for p a r a t h y r o i d l o c a l i z a t i o n irrespective o f surgical s t a t u s o r t u m o u r site. T h i s c o n t r a s t s w i t h the p e r f o r m a n c e o f u l t r a s o u n d a n d
MRI OF P A R A T H Y R O I D A D E N O M A S
thallium-technetium subtraction scintigraphy in patients with prior neck surgery or ectopic lesions. With ultrasound, sensitivities of 32 57% are typical in patients with previous neck surgery [5,21-24]. This is due to loss of the normal tissue planes in the neck and disruption of anatomical landmarks as well as the increased likelihood of ectopic adenomas in this group. Ultrasound is virtually useless for mediastinal adenomas because of the lack of an acoustic window. Thallium-technetium subtraction scintigraphy is also less effective in previously explored patients with sensitivities of 27-68% [5,24,25]. It is also less reliable with mediastinal lesions due to increased background activity and low photon energy [26,27]. Thus, these two techniques perform relatively poorly in the very patients in whom prior localization is of most value to the surgeon. Magnetic resonance imaging has shown high specificity for parathyroid adenoma detection in this series. This is a reflection of the high prevalence of hyperparathyroidism in the study group (100% by definition), and of the fact that normal parathyroid glands are generally not detected. In fact, all imaging techniques are liable to falsepositives from, for example, thyroid nodules and lymph nodes, and in a broader population would be relatively non-specific. Analysis of the false-negative M R I cases shows poor results with hyperptastic glands. Case 10 was a patient with renal failure in whom a left upper position adenoma was identified, but hyperplasia of left and right lower glands missed. The glands were relatively small, being 8 mm and 4 mm in maximum diameter respectively. Hyperplastic glands are generally smaller than adenomas and this no doubt explains their lower detection rate with all imaging techniques. A second patient (Case 11) had renal failure and hyperplasia in four glands, all undetected with M R I despite reasonable size. This patient had coronal STIR sequences only. The coronal STIR was generally considered difficult to interpret and was subsequently abandoned in favour of axial slices. On review of this case following surgery, two discrete high signal lesions were visible adjacent to the thyroid representing two o f the hyperplastic glands. The other patient with an hyperplastic gland (a solitary nodule in an ectopic position) was localized with MRI. The other two false-negative results were single adenomas which were visible in retrospect. One of these was the smallest gland in the series (470 mg), and the other falsenegative lesion was clearly visible on review. The detection rate was thus improved on second reading with increased experience and confidence in the technique. Of the two false-positive cases, the first had a rightsided adenoma (detected by MRI) removed at her second neck exploration. The STIR images showed a further putative lesion on the left but this area was not reexplored. Following surgery, the patient became normocalcaemie and has remained so. The latter M R I abnormality was therefore regarded as false-positive. This patient also had venous sampling which strongly localized to the right. On review of the M R images, the falsepositive lesion was attributed to asymmetry of a generally high-signal thyroid gland. In the second false-positive case, an unusual appearance of the left internal jugular vein was thought to represent a parathyroid adenoma. In general, falsepositives due to blood vessels should be unusual since: (a)
327
vessels can be traced across several slices and may show variable signal characteristics in different slices; (b) when they exhibit high signal, this is usually very intense, more so than tumours; and (c) they are usually accompanied by a motion artefact in the phase-encoding direction (Fig. 2). The overall sensitivity and specificity of M RI using the STIR sequence in conjunction with Tl-weighted SE sequences are comparable with the figures quoted in the literature for conventional M R I using T1- and T2weighted SE sequences [1-6]. This suggests that the two techniques are broadly equivalent. However, we have been unable directly to compare the performance of the STIR sequence for parathyroid adenoma detection with that ofT2-weighted SE sequences since the latter were not carried out in all cases. It is possible that the two techniques have specific strengths and weaknesses. For example, the STIR sequence, being a fat-suppression technique, is likely to be superior for lesions surrounded by fat since adenomas on T2-weighted SE sequences may be isointense with fat and therefore difficult to demonstrate [2,3,8,9]. This raises the question of whether sensitivity could be increased still further by the combination of fat-suppression sequences and T2-weighted scans. In conclusion, M R imaging using a fat-suppression technique (STIR) in conjunction with Tl-weighted sequences gives good results in an heterogeneous group of patients including previously operated patients and those with lesions in ectopic sites. The method as described is quick and straightforward and gives a comprehensive survey of neck and mediastinum in an average examination time of around 45 min. Magnetic resonance imaging using the STIR sequence is a valuable technique in the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism. Acknowledgements. This project was funded with a grant from the Bristol United Hospitals District Medical Research Committee. MRI facilities wereprovidedby the Bristol MRI ScannerFund and the Dawn James Trust. We thank the staff of the Bristol MRI Centre and the Department of Radiodiagnosis, Bristol Royal Infirmary, for tfieir professional assistance, and also Miss AudreyKellett for preparing the illustrations and Mrs Jan Stoddart for typing the manuscript.
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