SPECT/CT Fusion in the Diagnosis of Hyperparathyroidism

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SPECT/CT Fusion in the Diagnosis of Hyperparathyroidism Yoshio Monzen, Akihisa Tamura, Hajime Okazaki, Taichi Kurose, Masayuki Kobayashi, Masatsugu Kuraoka Department of Radiology, Hiroshima Prefectural Hospital, Hiroshima, Japan A R T I C L E I N F O Article type: Technical note Article history: Received: 2 Jun 2014 Revised: 24 Aug 2014 Accepted: 28 Aug 2014 Keywords: Tc-MIBI parathyroid scintigraphy Fusion image Hyperparathyroidism SPECT/CT A B S T R A C T Objective(s): In this study, we aimed to analyze the relationship between the diagnostic ability of fused single photon emission computed tomography/computed tomography (SPECT/CT) images in localization of parathyroid lesions and the size of adenomas or hyperplastic glands. Methods: Five patients with primary hyperparathyroidism (PHPT) and 4 patients with secondary hyperparathyroidism (SHPT) were imaged 15 and 120 minutes after the intravenous injection of technetiummethoxyisobutylisonitrile ( Tc-MIBI). All patients underwent surgery and 5 parathyroid adenomas and 10 hyperplastic glands were detected. Pathologic findings were correlated with imaging results. Results: The SPECT/CT fusion images were able to detect all parathyroid adenomas even with the greatest axial diameter of 0.6 cm. Planar scintigraphy and SPECT imaging could not detect parathyroid adenomas with an axial diameter of 1.0 to 1.2 cm. Four out of 10 (40%) hyperplastic parathyroid glands were diagnosed, using planar and SPECT imaging and 5 out of 10 (50%) hyperplastic parathyroid glands were localized, using SPECT/CT fusion images. Conclusion: SPECT/CT fusion imaging is a more useful tool for localization of parathyroid lesions, particularly parathyroid adenomas, in comparison with planar and or SPECT imaging. Please cite this paper as: Monzen Y, Tamura A, Okazaki H, Kurose T, Kobayashi M, Kuraoka M. SPECT/CT Fusion in the Diagnosis of Hyperparathyroidism. Introduction Technetium- methoxyisobutylisonitrile ( Tc-MIBI) parathyroid scintigraphy is a useful tool for localization of lesions in hyperparathyroidism (HPT). However, few reports have reviewed the diagnostic ability of single photon emission computed tomography/ computed tomography (SPECT/CT) imaging in HPT using fusion images. In the present study, we aimed to evaluate the correlation between the diagnostic ability of fused SPECT/CT images in localization of parathyroid lesions and the size of adenomas or hyperplastic glands. Methods Nine patients with HPT underwent MIBI using SPECT/CT imaging between May 2012 and April 2014. Five patients were diagnosed with primary hyperparathyroidism (PHPT) and 4 patients diagnosed with secondary hyperparathyroidism (SHPT) with chronic renal failure. All patients underwent surgery. Five lesions were identified as parathyroid adenomas, while 10 lesions were identified to be parathyroid hyperplasia. Parathyroid hormone and calcium levels remained within the normal range in 8 patients after the surgery, although parathyroid hormone * Corresponding author: Yoshio Monzen, Department of Radiology, Hiroshima Prefectural Hospital, 1-5-54 Ujinakanda Minami-ku, Hiroshima 734-8530 Japan. Tel +81 082-254-1818 Ext. 1000; Fax +81 082-253-8274; E-mail: monzen.so@s9.dion.ne.jp 2015 mums.ac.ir All rights reserved. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Monzen Y et al SPECT/CT Fusion of Hyperparathyroidism level increased after the surgery in 1 patient with PHPT. The SPECT/CT equipment used in this study was Symbia T16 (Siemens, USA), which combines 16-slice multidetector CT and SPECT. Six-hundred MBq of Tc-MIBI was injected intravenously in all patients. Early and delayed neck and upper thorax planar images were acquired 15 and 120 minutes after the injection, respectively. SPECT/ CT acquisition was performed immediately after obtaining the delayed planar images; SPECT images were obtained using the SPECT/CT system. Overall, 90 projections (128 128 matrix) were acquired (20 seconds each), with a total duration of 15 minutes for the whole SPECT/CT procedure. CT was performed immediately after SPECT imaging. The main CT parameters were 130 kv, 25 mas, and a 1.2 mm slice thickness; no intravenous contrast medium was used. SPECT/CT data were analyzed on a Syngo workstation, which provided transaxial, coronal, and sagittal slices of SPECT, CT, and fused SPECT-CT data. The size of the lesions was obtained from the pathology reports. Statistical analysis To compare the mean size of lesions in two groups, we used two-tailed student s t-test. For statistical analysis, Excel 2012 was used (SSRI Co., Ltd., Japan). P-value less than 0.05 was considered statistically significant. Results Five parathyroid adenomas and five hyperplastic glands were correctly localized, using the SPECT/CT fusion images. In contrast, 5 hyperplastic parathyroid glands could not be detected by fusion images. Three out of five parathyroid adenomas were localized on Tc-MIBI planar scintigraphy and SPECT images, whereas 5 parathyroid adenomas were localized on the SPECT/CT fusion images. All parathyroid adenomas with the largest axial diameter of 0.6 cm or more were localized on the SPECT/CT fusion images. In contrast, parathyroid adenomas with the greatest axial diameter of 1.0 to 1.2 cm were not localized on planar Tc-MIBI scintigraphy or SPECT images (Figure 1). Figure 1. A. Initial and delayed phases of planar Tc-MIBI scintigraphy showed increased activity in the left lobe (arrow). MIBI could not be used to differentiate between a parathyroid lesion and a thyroid lesion. B. Axial non-contrast enhanced CT of the neck. A lesion was detected posterior to the left lobe of the thyroid (arrow). C. Fusion axial image of SPECT/CT. The radiotracer accumulated in the lesion posterior to the left lobe of the thyroid (arrow). Adenoma of the left lower parathyroid gland was removed during surgery 62

SPECT/CT Fusion of Hyperparathyroidism Monzen Y et al The mean size of the detected and undetected parathyroid adenomas in planar scintigraphy was 1.3±0.6 and 1.1±0.1 cm, respectively (P=0.7). The corresponding values were 1.3±0.6 and 1.1±0.1 cm in SPECT imaging, respectively (P =0.7). The mean size of detected adenomas was 1.2±0.4 cm, based on the SPECT/CT images, and no adenoma remained undetected, using SPECT/CT images. Four out of 10 (40%) hyperplastic parathyroid glands were localized, using planar Tc-MIBI scintigraphy and SPECT images, while 5 out of 10 (50%) hyperplastic parathyroid glands were localized, using the SPECT/CT fusion images. Five hyperplastic parathyroid glands with the greatest axial diameter of > 0.4 cm were correctly localized, using the SPECT/CT fusion images. The mean size of 5 hyperplastic parathyroid glands detected on SPECT/CT fusion images was 0.6±0.2 cm (range 0.4 0.9cm). Five scintigraphically undetected hyperplastic parathyroid glands had the mean greatest axial diameter of 0.6±0.3 cm (range: 0.4-1.1 cm); there was not a statistically significant difference between the two groups (P=1.0). Although this negative result may reflect the small sample size in our study, it seems that other factors may play a role in the detection of hyperplastic glands, using scintigraphy (Table 1). Figure 1 shows a patient with PHPT due to left inferior parathyroid adenoma, which is not localized by planar scintigraphy, while detected by SPECT/CT imaging. Figure 2 shows a patient with SHPT due to right inferior hyperplastic parathyroid gland, which is not localized using planar scintigraphy, while detected by SPECT/CT imaging. Discussion The main advantage of SPECT/CT systems is their application for the acquisition of highprecision fusion images, using both CT and SPECT imaging. Fusion images can be used for making a differential diagnosis between benign and malignant diseases in different body organs, determining the stage of the lesion, confirming a metastasis or its recurrence, and selecting a Figure 2. A. Initial and delayed phases of Tc-MIBI planar scintigraphy showed abnormal uptake. B. Coronal non-contrast enhanced CT of the neck. A lesion was detected in the inferior right portion of the thyroid lobe (arrow). A cystic mass was detected in the left lobe of the thyroid (arrowhead). C. A coronal fused image (SPECT/CT). The fusion image demonstrated a faint abnormal uptake of Tc-MIBI in the inferior right portion of the thyroid lobe (arrow). Right inferior hyperplastic parathyroid gland was removed during surgery 63

Monzen Y et al SPECT/CT Fusion of Hyperparathyroidism Table 1. Characteristics of the patients and detection of lesions using Tc-MIBI planar, SPECT and SPECT/CT fusion image Patient Age Sex Pathology Localization of the lesions Size of lesions (cm) Planar SPECT SPECT/CT 1 75 M A LIPG 1.0 3.5 2 64 F A 1.5 1.7 3 30 F A LIPG 0.6 1.4 4 62 F A 1.2 1.4 5 63 M A LIPG 1.7 1.3 6 45 F H 7 75 F H 8 54 M H 9 46 F H RSPG RSPG 0.6 1.3 0.4 0.8 0.4 0.5 0.5 1.1 0.7 1.2 1.1 1.4 0.4 0.4 0.4 0.9 0.4 0.6 0.9 1.2 A : Adenoma, H : Hyperplasia, M : Male, F : Female : Left superior parathyroid gland LIPG : Left inferior parathyroid gland RSPG : Right superior parathyroid gland : Right inferior parathyroid gland Size of the lesion : Greatest axial diameter x cranio-caudal length treatment strategy. SPECT/CT imaging can be also used to clarify the existence of an abnormal uptake, based on the diminution of scattered radiation (1, 2). Although planar Tc-MIBI has been used in localization of parathyroid adenomas or hyperplasia, it is not always easy to detect these lesions in the delayed phase. In this regard, Shafiei et al. investigated the diagnostic ability of Tcsestamibi parathyroid SPECT/CT imaging in 48 patients with PHPT. The sensitivity and specificity of SPECT/CT for localization of parathyroid adenomas were 78% and 97%, respectively. These results indicate that SPECT/CT is a useful tool for localizing parathyroid adenomas (3). Ciappuccini et al. analyzed 94 patients with PHPT. In their study, dual-phase Tc-sestamibi scintigraphy with SPECT/CT enabled the diagnosis of parathyroid adenomas in 56 out of 94 patients (63%) with PHPT (4). Furthermore, Papathyanassion et al. and Li et al. reported that Tc-MIBI SPECT/CT is useful in detecting an ectopic parathyroid gland in patients with HPT (5, 6). Meanwhile, Torregrosa et al. performed Tc- MIBI scintigraphy in patients with PHPT (n=16) and SHPT (n=22) and found 93% and 54% sensitivities for lesion localization in cases with PHPT and SHPT, respectively. They found that Tc-MIBI planar scintigraphy can be used as the imaging technique of choice for preoperative localization of an abnormal parathyroid gland in patients with PHPT, but only as a complementary imaging technique in patients with SHPT (7). In addition, Caldarella et al. reviewed 24 studies on 471 patients with SHPT, using Tc- MIBI planar images. The sensitivity and specificity of Tc-MIBI planar scintigraphy in detecting hyperplastic glands in SHPT patients were 58% and 93%, respectively. Considering the inadequate diagnostic accuracy of this technique, it should not be considered a first-line diagnostic imaging method for preoperative localization in patients with SHPT (8). In the present study, the detection rate of hyperplastic parathyroid glands, using Tc- MIBI planar or fusion imaging, was poor. The degree of Tc-MIBI uptake in parathyroid gland is influenced by the content of mitochondria-rich oxyphil cells. It is thought that Tc-MIBI easily accumulates in parathyroid adenomas, which contain many oxyphil cells (9, 10). In our study, the detection rate of hyperplastic gland, using Tc-MIBI planar, SPECT, and fusion imaging was poor. Although Tc-MIBI planar scintigraphy was not successful in the localization of hyperplastic glands, in patient. 6, fusion images were effective in the localization of hyperplastic gland with a faint abnormal uptake of Tc-MIBI in the right lower parathyroid (Figure 2). previous studies have evaluated the correlation between the diagnostic ability of fusion images and the size of parathyroid lesions 64

SPECT/CT Fusion of Hyperparathyroidism Monzen Y et al or hyperplastic glands, based on pathological evaluations. In the current study, size of lesions in pathological evaluations was used for making comparisons. It showed that fusion images could detect parathyroid adenomas with the greatest axial diameter of > 0.6 cm, while planar Tc-MIBI scintigraphy and SPECT imaging were unable to detect parathyroid adenomas with the largest axial diameter of 1.0-1.2 cm. It can be concluded that SPECT/CT fusion imaging is a more useful tool for the localization of parathyroid lesions in hyperparathyroidism, especially parathyroid adenomas, in comparison with planar Tc-MIBI parathyroid scintigraphy or SPECT imaging. Conflicts of interest ne of the authors have a direct or indirect financial interest in the products under investigation or the subject matter discussed in the article. References 1. Utsunomiya D, Shiraishi S, Imuta M, Tomiguchi S, Kawanaka K, Morishita S, et al. Added value of SPECT/CT fusion in assessing suspected bone metastasis: comparison with scintigraphy alone and nonfused scintigraphy and CT. Radiology. 2006; 238:264-71. 2. Even-SapirE, Flusser G, Lerman H, Lievshitz G, Metser U. SPECT/multislice low-dose CT: a clinically relevant constituent in the imaging algorithm of nononcologic patients referred for bone scintigraphy. J Nucl Med. 2007;48:319-24. 3. Shafiei B, Hoseinzadeh S, Fotouhi F, Malek H, Azizi F, Jahed A, et al. Preoperative Tcsestamibi scintigraphy in patients with primary hyperparathyroidism and concomitant nodular goiter: comparison of SPECT-CT, SPECT, and planar imaging. Nucl Med commun. 2012; 33:1070-6. 4. Ciappuccini R, Morera J, Pascal P, Rame JP, Heutte N, Aide N, et al. Dual-phase Tc-sestamibi scintigraphy with neck and thorax SPECT/CT in primary hyperparathyroidism: a single-institution experience. Clin Nucl Med.2012;37:223-8. 5. Papathanassiou D, Flament JB, Pochart JM, Patey M, Marty H, Liehn JC, et al. SPECT/CT in localization of parathyroid adenoma or hyperplasia in patients with previous neck surgery. Clin Nucl Med. 2008; 33: 394-7. 6. Li L, Chen L, Yang Y, Han J, Wu s, Bao Y, et al. Giant anterior mediastinal parathyroid adenoma. Clin Nucl Med. 2012; 37: 889-91. 7. Torregrosa JV, Palomar MR, Pons F, Sabater L, Gilabert R, LIovera J, et al. Has double-phase MIBI scintigraphy usefulness in the diagnosis of hayperparathyroidism?. Nephrol Dial Transplant. 1998; 13: 37-40. 8. Caldarella C, Treglia G, Pontecorvi A, Giordano A. Diagnostic performance of planar scintigraphy using Tc-MIBI in patients with secondary hyperparathyroidism: a meta-analysis. Ann Nucl Med. 2012; 26: 794-803. 9. Carpentier A, Jeannotte S, Verreault J, Lefebvre B, Bisson G, Mongeau CJ, et al. Preoperative localization of parathyroid lesions in hyperparathyroidism: relationship between Technetium--MIBI uptake and oxyphil cell count. J Nucl Med. 1998; 39: 1441-4. 10. Erbil Y, Kapran Y, Işsever H, Barbaros U, Adalet I, Dizdaroğlu F, et al. The positive effect of adenoma weight and oxyphil cell content on preoperative localization with Tc-sestamibi scanning for primary hyperparathyroidism. Am J Surg. 2008; 195: 34-39. 65